{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T02:55:52Z","timestamp":1785034552409,"version":"3.55.0"},"reference-count":242,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T00:00:00Z","timestamp":1634428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Androgen deprivation therapy (ADT) for metastatic and high-risk prostate cancer (PC) inhibits growth pathways driven by the androgen receptor (AR). Over time, ADT leads to the emergence of lethal castrate-resistant PC (CRPC), which is consistently caused by an acquired ability of tumors to re-activate AR. This has led to the development of second-generation anti-androgens that more effectively antagonize AR, such as enzalutamide (ENZ). However, the resistance of CRPC to ENZ develops rapidly. Studies utilizing preclinical models of PC have established that inhibition of the Jak2-Stat5 signaling leads to extensive PC cell apoptosis and decreased tumor growth. In large clinical cohorts, Jak2-Stat5 activity predicts PC progression and recurrence. Recently, Jak2-Stat5 signaling was demonstrated to induce ENZ-resistant PC growth in preclinical PC models, further emphasizing the importance of Jak2-Stat5 for therapeutic targeting for advanced PC. The discovery of the Jak2V617F somatic mutation in myeloproliferative disorders triggered the rapid development of Jak1\/2-specific inhibitors for a variety of myeloproliferative and auto-immune disorders as well as hematological malignancies. Here, we review Jak2 inhibitors targeting the mutated Jak2V617F vs. wild type (WT)-Jak2 that are currently in the development pipeline. Among these 35 compounds with documented Jak2 inhibitory activity, those with potency against WT-Jak2 hold strong potential for advanced PC therapy.<\/jats:p>","DOI":"10.3390\/cancers13205204","type":"journal-article","created":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T23:13:32Z","timestamp":1634512412000},"page":"5204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Second-Generation Jak2 Inhibitors for Advanced Prostate Cancer: Are We Ready for Clinical Development?"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6040-9236","authenticated-orcid":false,"given":"Paul","family":"Beinhoff","sequence":"first","affiliation":[{"name":"Department of Pathology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavannya","family":"Sabharwal","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Pharmacology and Toxicology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Prostate Cancer Center of Excellence at the Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vindhya","family":"Udhane","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Pharmacology and Toxicology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Prostate Cancer Center of Excellence at the Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Maranto","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Pharmacology and Toxicology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Prostate Cancer Center of Excellence at the Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"LaViolette","sequence":"additional","affiliation":[{"name":"Prostate Cancer Center of Excellence at the Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Radiology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth M.","family":"Jacobsohn","sequence":"additional","affiliation":[{"name":"Prostate Cancer Center of Excellence at the Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Urology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Surgical Oncology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth A.","family":"Iczkowski","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Prostate Cancer Center of Excellence at the Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9364-8572","authenticated-orcid":false,"given":"Liang","family":"Wang","sequence":"additional","affiliation":[{"name":"Prostate Cancer Center of Excellence at the Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Tumor Biology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Hall","sequence":"additional","affiliation":[{"name":"Prostate Cancer Center of Excellence at the Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Surgery, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Dehm","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Kilari","sequence":"additional","affiliation":[{"name":"Prostate Cancer Center of Excellence at the Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marja T.","family":"Nevalainen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Pharmacology and Toxicology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Prostate Cancer Center of Excellence at the Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,17]]},"reference":[{"key":"ref_1","unstructured":"American Cancer Society (2021, April 10). Cancer Facts & Figures 2019. Available online: https:\/\/www.cancer.org\/research\/cancer-facts-statistics\/all-cancer-facts-figures\/cancer-facts-figures-2019.html."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1002\/1097-0142(19930201)71:3+<1059::AID-CNCR2820711426>3.0.CO;2-6","article-title":"Combination therapy for prostate cancer. Endocrine and biologic basis of its choice as new standard first-line therapy","volume":"71","author":"Labrie","year":"1993","journal-title":"Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nrclinonc.2011.117","article-title":"The changing therapeutic landscape of castration-resistant prostate cancer","volume":"8","author":"Yap","year":"2011","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/nrclinonc.2014.72","article-title":"Evolution of androgen receptor targeted therapy for advanced prostate cancer","volume":"11","author":"Wong","year":"2014","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/S0140-6736(14)61947-4","article-title":"Prostate cancer","volume":"387","author":"Attard","year":"2016","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1001\/jama.2017.7248","article-title":"The Diagnosis and Treatment of Prostate Cancer: A Review","volume":"317","author":"Litwin","year":"2017","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"26321","DOI":"10.1074\/jbc.M203310200","article-title":"Bicalutamide functions as an androgen receptor antagonist by assembly of a transcriptionally inactive receptor","volume":"277","author":"Masiello","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1056\/NEJMoa1405095","article-title":"Enzalutamide in metastatic prostate cancer before chemotherapy","volume":"371","author":"Beer","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6067","DOI":"10.1158\/1078-0432.CCR-13-1763","article-title":"Enzalutamide for treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel: U.S. Food and Drug Administration drug approval summary","volume":"19","author":"Ning","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.eururo.2016.07.032","article-title":"Enzalutamide in Men with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer: Extended Analysis of the Phase 3 PREVAIL Study","volume":"71","author":"Beer","year":"2017","journal-title":"Eur. Urol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1634\/theoncologist.2015-0166","article-title":"Food and Drug Administration Approval Summary: Enzalutamide for the Treatment of Patients With Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer","volume":"20","author":"Ning","year":"2015","journal-title":"Oncologist"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1126\/science.1168175","article-title":"Development of a second-generation antiandrogen for treatment of advanced prostate cancer","volume":"324","author":"Tran","year":"2009","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.2147\/OTT.S147168","article-title":"Profile of apalutamide in the treatment of metastatic castration-resistant prostate cancer: Evidence to date","volume":"11","author":"Chong","year":"2018","journal-title":"Onco Targets Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"380","DOI":"10.5489\/cuaj.10167","article-title":"Guidelines for the management of castrate-resistant prostate cancer","volume":"4","author":"Saad","year":"2010","journal-title":"Can. Urol. Assoc. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/nrurol.2014.243","article-title":"Emerging mechanisms of enzalutamide resistance in prostate cancer","volume":"11","author":"Claessens","year":"2014","journal-title":"Nat. Rev. Urol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrc4016","article-title":"Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer","volume":"15","author":"Watson","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1056\/NEJMoa1315815","article-title":"AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer","volume":"371","author":"Antonarakis","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5469","DOI":"10.1158\/0008-5472.CAN-08-0594","article-title":"Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance","volume":"68","author":"Dehm","year":"2008","journal-title":"Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1016\/j.cell.2013.11.012","article-title":"Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade","volume":"155","author":"Arora","year":"2013","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1158\/2159-8290.CD-13-0226","article-title":"A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509","volume":"3","author":"Joseph","year":"2013","journal-title":"Cancer Discov."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1158\/2159-8290.CD-13-0142","article-title":"An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide)","volume":"3","author":"Korpal","year":"2013","journal-title":"Cancer Discov."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nm.4045","article-title":"Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer","volume":"22","author":"Beltran","year":"2016","journal-title":"Nat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"474e476","DOI":"10.1016\/j.ccell.2017.09.003","article-title":"Androgen Receptor Pathway-Independent Prostate Cancer Is Sustained through FGF Signaling","volume":"32","author":"Bluemn","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1158\/1535-7163.MCT-19-0508","article-title":"Enzalutamide-Induced Feed-Forward Signaling Loop Promotes Therapy-Resistant Prostate Cancer Growth Providing an Exploitable Molecular Target for Jak2 Inhibitors","volume":"19","author":"Udhane","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.1600-065X.2008.00754.x","article-title":"Janus kinases in immune cell signaling","volume":"228","author":"Ghoreschi","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3388","DOI":"10.1182\/blood-2015-01-621110","article-title":"Molecular insights into regulation of JAK2 in myeloproliferative neoplasms","volume":"125","author":"Silvennoinen","year":"2015","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"24076","DOI":"10.1016\/S0021-9258(18)35948-9","article-title":"Prolactin receptor triggering. Evidence for rapid tyrosine kinase activation","volume":"267","author":"Rui","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1210\/endo.135.4.7925093","article-title":"JAK2 activation and cell proliferation induced by antibody-mediated prolactin receptor dimerization","volume":"135","author":"Rui","year":"1994","journal-title":"Endocrinology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3089","DOI":"10.1210\/en.2006-1761","article-title":"Autocrine prolactin promotes prostate cancer cell growth via Janus kinase-2-signal transducer and activator of transcription-5a\/b signaling pathway","volume":"148","author":"Dagvadorj","year":"2007","journal-title":"Endocrinology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1016\/j.ajpath.2015.04.026","article-title":"Jak2-Stat5a\/b Signaling Induces Epithelial-to-Mesenchymal Transition and Stem-Like Cell Properties in Prostate Cancer","volume":"185","author":"Talati","year":"2015","journal-title":"Am. J. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4774","DOI":"10.1158\/0008-5472.CAN-03-3499","article-title":"Activation of signal transducer and activator of transcription 5 in human prostate cancer is associated with high histological grade","volume":"64","author":"Li","year":"2004","journal-title":"Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/nrm909","article-title":"Stats: Transcriptional control and biological impact","volume":"3","author":"Levy","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1158\/1078-0432.CCR-12-0284","article-title":"Molecular pathways: Jak\/STAT pathway: Mutations, inhibitors, and resistance","volume":"19","author":"Verstovsek","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0955-0674(00)00199-X","article-title":"The Stat family in cytokine signaling","volume":"13","author":"Ihle","year":"2001","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8831","DOI":"10.1073\/pnas.92.19.8831","article-title":"Cloning and expression of Stat5 and an additional homologue (Stat5b) involved in prolactin signal transduction in mouse mammary tissue","volume":"92","author":"Liu","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","first-page":"1496","article-title":"Activation of Stat5a and Stat5b by tyrosine phosphorylation is tightly linked to mammary gland differentiation","volume":"10","author":"Liu","year":"1996","journal-title":"Mol. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj20030407","article-title":"Principles of interleukin (IL)-6-type cytokine signalling and its regulation","volume":"374","author":"Heinrich","year":"2003","journal-title":"Biochem. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3375","DOI":"10.1172\/JCI57158","article-title":"Therapeutic strategies for the clinical blockade of IL-6\/gp130 signaling","volume":"121","author":"Jones","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Pestell, R.G., and Nevalainen, M.T. (2008). Prostate Cancer: Signaling Networks, Genetics, and New Treatment Strategies, Humana Press.","DOI":"10.1007\/978-1-60327-079-3"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1126\/science.3136546","article-title":"Cloning and expression of the human interleukin-6 (BSF-2\/IFN beta 2) receptor","volume":"241","author":"Yamasaki","year":"1988","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0092-8674(95)90311-9","article-title":"Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation","volume":"82","author":"Wen","year":"1995","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"27287","DOI":"10.1074\/jbc.M304307200","article-title":"Inhibition of transcription factor Stat5 induces cell death of human prostate cancer cells","volume":"278","author":"Ahonen","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1158\/1078-0432.CCR-07-2024","article-title":"Transcription factor signal transducer and activator of transcription 5 promotes growth of human prostate cancer cells in vivo","volume":"14","author":"Dagvadorj","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.2353\/ajpath.2010.090653","article-title":"Transcription factor Stat3 stimulates metastatic behavior of human prostate cancer cells in vivo, whereas Stat5b has a preferential role in the promotion of prostate cancer cell viability and tumor growth","volume":"176","author":"Gu","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1677\/ERC-09-0328","article-title":"Stat5 promotes metastatic behavior of human prostate cancer cells in vitro and in vivo","volume":"17","author":"Gu","year":"2010","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1158\/1535-7163.MCT-14-0883","article-title":"Structure-Based Screen Identifies a Potent Small Molecule Inhibitor of Stat5a\/b with Therapeutic Potential for Prostate Cancer and Chronic Myeloid Leukemia","volume":"14","author":"Liao","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5658","DOI":"10.1158\/1078-0432.CCR-13-0422","article-title":"Pharmacologic inhibition of Jak2-Stat5 signaling By Jak2 inhibitor AZD1480 potently suppresses growth of both primary and castrate-resistant prostate cancer","volume":"19","author":"Gu","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_48","first-page":"8757","article-title":"Activation of signal transducer and activator of transcription 5 is required for progression of autochthonous prostate cancer: Evidence from the transgenic adenocarcinoma of the mouse prostate system","volume":"63","author":"Kazansky","year":"2003","journal-title":"Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3724","DOI":"10.18632\/oncotarget.12554","article-title":"Androgen receptor-dependent and-independent mechanisms driving prostate cancer progression: Opportunities for therapeutic targeting from multiple angles","volume":"8","author":"Hoang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1158\/1535-7163.MCT-10-0850","article-title":"Transcription factor Stat5 knockdown enhances androgen receptor degradation and delays castration-resistant prostate cancer progression in vivo","volume":"10","author":"Thomas","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Maranto, C., Udhane, V., Jia, J., Verma, R., Muller-Newen, G., LaViolette, P.S., Pereckas, M., Sabharwal, L., Terhune, S., and Pattabiraman, N. (2020). Prospects for Clinical Development of Stat5 Inhibitor IST5-002: High Transcriptomic Specificity in Prostate Cancer and Low Toxicity In Vivo. Cancers, 12.","DOI":"10.3390\/cancers12113412"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1016\/j.ajpath.2013.02.044","article-title":"STAT5A\/B gene locus undergoes amplification during human prostate cancer progression","volume":"182","author":"Haddad","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5863","DOI":"10.1158\/1078-0432.CCR-05-0562","article-title":"Activation of signal transducer and activator of transcription-5 in prostate cancer predicts early recurrence","volume":"11","author":"Li","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.humpath.2012.06.001","article-title":"Nuclear Stat5a\/b predicts early recurrence and prostate cancer-specific death in patients treated by radical prostatectomy","volume":"44","author":"Mirtti","year":"2013","journal-title":"Hum. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1158\/1055-9965.EPI-18-1358","article-title":"Positive STAT5 Protein and Locus Amplification Status Predicts Recurrence after Radical Prostatectomy to Assist Clinical Precision Management of Prostate Cancer","volume":"28","author":"Haddad","year":"2019","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1002\/jcb.24473","article-title":"Differential effects of exogenous and autocrine growth hormone on LNCaP prostate cancer cell proliferation and survival","volume":"114","author":"Nakonechnaya","year":"2013","journal-title":"J. Cell Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3109\/07435800.2014.966383","article-title":"Growth hormone enhances LNCaP prostate cancer cell motility","volume":"40","author":"Nakonechnaya","year":"2015","journal-title":"Endocr. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"110445","DOI":"10.1016\/j.mce.2019.05.004","article-title":"Growth hormone (GH) receptor (GHR)-specific inhibition of GH-Induced signaling by soluble IGF-1 receptor (sol IGF-1R)","volume":"492","author":"Zhang","year":"2019","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.pharmthera.2017.05.009","article-title":"Prolactin receptor targeting in breast and prostate cancers: New insights into an old challenge","volume":"179","author":"Goffin","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"15199","DOI":"10.1073\/pnas.0911651107","article-title":"Local prolactin is a target to prevent expansion of basal\/stem cells in prostate tumors","volume":"107","author":"Rouet","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/978-3-319-12114-7_10","article-title":"Prolactin-induced prostate tumorigenesis","volume":"846","author":"Goffin","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1210\/me.2013-1178","article-title":"IGF-1R modulation of acute GH-induced STAT5 signaling: Role of protein tyrosine phosphatase activity","volume":"27","author":"Gan","year":"2013","journal-title":"Mol. Endocrinol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1158\/1541-7786.MCR-08-0243","article-title":"An erythropoietin autocrine\/paracrine axis modulates the growth and survival of human prostate cancer cells","volume":"7","author":"Jeong","year":"2009","journal-title":"Mol. Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/sj.onc.1209814","article-title":"Neurotensin stimulates mitogenesis of prostate cancer cells through a novel c-Src\/Stat5b pathway","volume":"26","author":"Amorino","year":"2007","journal-title":"Oncogene"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/pros.20310","article-title":"Erythropoietin stimulates growth and STAT5 phosphorylation in human prostate epithelial and prostate cancer cells","volume":"66","author":"Feldman","year":"2006","journal-title":"Prostate"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1210\/endo.143.1.8576","article-title":"PRL signal transduction in the epithelial compartment of rat prostate maintained as long-term organ cultures in vitro","volume":"143","author":"Ahonen","year":"2002","journal-title":"Endocrinology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5412","DOI":"10.1210\/endo.140.11.7090","article-title":"Prolactin is a survival factor for androgen-deprived rat dorsal and lateral prostate epithelium in organ culture","volume":"140","author":"Ahonen","year":"1999","journal-title":"Endocrinology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1096\/fasebj.11.14.9409549","article-title":"Androgen-dependent expression of prolactin in rat prostate epithelium in vivo and in organ culture","volume":"11","author":"Nevalainen","year":"1997","journal-title":"FASEB J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3078","DOI":"10.1210\/endo.137.7.8770934","article-title":"Expression and hormone regulation of prolactin receptors in rat dorsal and lateral prostate","volume":"137","author":"Nevalainen","year":"1996","journal-title":"Endocrinology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1172\/JCI119204","article-title":"Prolactin and prolactin receptors are expressed and functioning in human prostate","volume":"99","author":"Nevalainen","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1210\/endo-129-2-612","article-title":"Estrogen and prolactin regulation of rat dorsal and lateral prostate in organ culture","volume":"129","author":"Nevalainen","year":"1991","journal-title":"Endocrinology"},{"key":"ref_72","first-page":"6659","article-title":"Constitutive activation of Stat3 in human prostate tumors and cell lines: Direct inhibition of Stat3 signaling induces apoptosis of prostate cancer cells","volume":"62","author":"Mora","year":"2002","journal-title":"Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0002-9440(10)63940-5","article-title":"Increased expression of the interleukin-11 receptor and evidence of STAT3 activation in prostate carcinoma","volume":"158","author":"Campbell","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1476-4598-4-2","article-title":"Stable expression of constitutively-activated STAT3 in benign prostatic epithelial cells changes their phenotype to that resembling malignant cells","volume":"4","author":"Huang","year":"2005","journal-title":"Mol. Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/pros.10079","article-title":"Stat3 activation in prostatic carcinomas","volume":"51","author":"Dhir","year":"2002","journal-title":"Prostate"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.urology.2005.03.066","article-title":"Clinical and pathologic significance of activation of signal transducer and activator of transcription 3 in prostate cancer","volume":"66","author":"Horinaga","year":"2005","journal-title":"Urology"},{"key":"ref_77","first-page":"2132","article-title":"Interleukin 6 activates androgen receptor-mediated gene expression through a signal transducer and activator of transcription 3-dependent pathway in LNCaP prostate cancer cells","volume":"60","author":"Chen","year":"2000","journal-title":"Cancer Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1006\/bbrc.2001.4758","article-title":"Cross-talk between signal transducer and activator of transcription 3 and androgen receptor signaling in prostate carcinoma cells","volume":"283","author":"Matsuda","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"7076","DOI":"10.1074\/jbc.M108255200","article-title":"Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways","volume":"277","author":"Ueda","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/S0006-291X(03)00792-7","article-title":"Interleukin-6 differentially regulates androgen receptor transactivation via PI3K-Akt, STAT3, and MAPK, three distinct signal pathways in prostate cancer cells","volume":"305","author":"Yang","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1158\/1535-7163.11.3.1","article-title":"Signal transducer and activator of transcription 3 (STAT3) activation in prostate cancer: Direct STAT3 inhibition induces apoptosis in prostate cancer lines","volume":"3","author":"Barton","year":"2004","journal-title":"Mol. Cancer Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/pros.10110","article-title":"Stat3 enhances the growth of LNCaP human prostate cancer cells in intact and castrated male nude mice","volume":"52","author":"DeMiguel","year":"2002","journal-title":"Prostate"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/(SICI)1097-0045(20000215)42:3<239::AID-PROS10>3.0.CO;2-G","article-title":"Interleukin-6 induces prostate cancer cell growth accompanied by activation of stat3 signaling pathway","volume":"42","author":"Lou","year":"2000","journal-title":"Prostate"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1158\/1535-7163.MCT-13-0605","article-title":"Pharmacologic suppression of JAK1\/2 by JAK1\/2 inhibitor AZD1480 potently inhibits IL-6-induced experimental prostate cancer metastases formation","volume":"13","author":"Gu","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.2353\/ajpath.2008.071054","article-title":"Stat3 promotes metastatic progression of prostate cancer","volume":"172","author":"Abdulghani","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_86","unstructured":"Nevalainen, P. (2008). Transcription factors Stat5 and Stat3: Survival Factors for Prostate Cancer Cells. Prostate Cancer: Signaling Networks, Genetics and New Treatment Strategies, Springer."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/1096-9896(2000)9999:9999<::AID-PATH633>3.0.CO;2-X","article-title":"Immunohistochemical localization of interleukin-6 and its receptor in benign, premalignant and malignant prostate tissue","volume":"191","author":"Hobisch","year":"2000","journal-title":"J. Pathol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/path.1476","article-title":"Immunohistochemical analysis of the IL-6 family of cytokines and their receptors in benign, hyperplastic, and malignant human prostate","volume":"202","author":"Royuela","year":"2004","journal-title":"J. Pathol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/(SICI)1097-0045(19991001)41:2<127::AID-PROS7>3.0.CO;2-H","article-title":"Circulating levels of interleukin-6 in patients with hormone refractory prostate cancer","volume":"41","author":"Drachenberg","year":"1999","journal-title":"Prostate"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1158\/1078-0432.CCR-04-1560","article-title":"The prognostic significance of plasma interleukin-6 levels in patients with metastatic hormone-refractory prostate cancer: Results from cancer and leukemia group B 9480","volume":"11","author":"George","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1038\/sj.bjc.6601814","article-title":"Serum levels of IL-6 and TNF-alpha correlate with clinicopathological features and patient survival in patients with prostate cancer","volume":"90","author":"Michalaki","year":"2004","journal-title":"Br. J. Cancer"},{"key":"ref_92","first-page":"2702","article-title":"Serum interleukin 6 as a prognostic factor in patients with prostate cancer","volume":"6","author":"Nakashima","year":"2000","journal-title":"Clin. Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/S0090-4295(01)01405-4","article-title":"Plasma levels of interleukin-6 and its soluble receptor are associated with prostate cancer progression and metastasis","volume":"58","author":"Shariat","year":"2001","journal-title":"Urology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/S0090-4295(99)80034-X","article-title":"Interleukin-6: A candidate mediator of human prostate cancer morbidity","volume":"45","author":"Twillie","year":"1995","journal-title":"Urology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/S0022-5347(05)67289-8","article-title":"Cytokine variations in patients with hormone treated prostate cancer","volume":"164","author":"Wise","year":"2000","journal-title":"J. Urol."},{"key":"ref_96","first-page":"2941","article-title":"Prostate cancer cells (LNCaP) generated after long-term interleukin-6 treatment express interleukin-6 and acquire an interleukin-6-partially resistant phenotype","volume":"7","author":"Hobisch","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.1182\/blood-2005-05-1898","article-title":"The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia","volume":"106","author":"Levine","year":"2005","journal-title":"Blood"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.ccr.2005.03.023","article-title":"Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis","volume":"7","author":"Levine","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1056\/NEJMoa051113","article-title":"A gain-of-function mutation of JAK2 in myeloproliferative disorders","volume":"352","author":"Kralovics","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/S0140-6736(05)71142-9","article-title":"Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders","volume":"365","author":"Baxter","year":"2005","journal-title":"Lancet"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/nature03546","article-title":"A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera","volume":"434","author":"James","year":"2005","journal-title":"Nature"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1158\/1078-0432.CCR-13-0279","article-title":"Molecular pathways: Molecular basis for sensitivity and resistance to JAK kinase inhibitors","volume":"20","author":"Meyer","year":"2014","journal-title":"Clin Cancer Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ccell.2015.06.006","article-title":"CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms","volume":"28","author":"Meyer","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1634\/theoncologist.2013-0198","article-title":"AZD1480: A phase I study of a novel JAK2 inhibitor in solid tumors","volume":"18","author":"Plimack","year":"2013","journal-title":"Oncologist"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1158\/1078-0432.CCR-11-3145","article-title":"Ruxolitinib: The first FDA approved therapy for the treatment of myelofibrosis","volume":"18","author":"Mascarenhas","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"14538","DOI":"10.1038\/srep14538","article-title":"Targeting substrate-site in Jak2 kinase prevents emergence of genetic resistance","volume":"5","author":"Kesarwani","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2147\/JEP.S110702","article-title":"Comprehensive kinase profile of pacritinib, a nonmyelosuppressive Janus kinase 2 inhibitor","volume":"8","author":"Singer","year":"2016","journal-title":"J. Exp. Pharmacol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1038\/leu.2011.175","article-title":"The novel JAK inhibitor CYT387 suppresses multiple signalling pathways, prevents proliferation and induces apoptosis in phenotypically diverse myeloma cells","volume":"25","author":"Monaghan","year":"2011","journal-title":"Leukemia"},{"key":"ref_109","first-page":"318","article-title":"The mechanism of action of tofacitinib\u2014An oral Janus kinase inhibitor for the treatment of rheumatoid arthritis","volume":"34","author":"Hodge","year":"2016","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"82","DOI":"10.12688\/f1000research.13167.1","article-title":"JAK inhibitors for the treatment of myeloproliferative neoplasms and other disorders","volume":"7","author":"Vainchenker","year":"2018","journal-title":"F1000Res"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1182\/blood-2009-04-214957","article-title":"Preclinical characterization of the selective JAK1\/2 inhibitor INCB018424: Therapeutic implications for the treatment of myeloproliferative neoplasms","volume":"115","author":"Vaddi","year":"2010","journal-title":"Blood"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1056\/NEJMoa1002028","article-title":"Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis","volume":"363","author":"Verstovsek","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/nbt0112-3","article-title":"Incyte comes of age with JAK inhibitor approval","volume":"30","author":"Moran","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/leu.2011.255","article-title":"Kinase domain mutations confer resistance to novel inhibitors targeting JAK2V617F in myeloproliferative neoplasms","volume":"26","author":"Deshpande","year":"2012","journal-title":"Leukemia"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1002\/jcph.354","article-title":"The pharmacokinetics, pharmacodynamics, and safety of baricitinib, an oral JAK 1\/2 inhibitor, in healthy volunteers","volume":"54","author":"Shi","year":"2014","journal-title":"J. Clin. Pharmacol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1056\/NEJMoa1110556","article-title":"JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis","volume":"366","author":"Harrison","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/leu.2016.323","article-title":"Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis","volume":"31","author":"Harrison","year":"2017","journal-title":"Leukemia"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"821","DOI":"10.3324\/haematol.2016.143644","article-title":"Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the RESPONSE trial","volume":"101","author":"Verstovsek","year":"2016","journal-title":"Haematologica"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1177\/0091270011405663","article-title":"The effect of CYP3A4 inhibition or induction on the pharmacokinetics and pharmacodynamics of orally administered ruxolitinib (INCB018424 phosphate) in healthy volunteers","volume":"52","author":"Shi","year":"2012","journal-title":"J. Clin. Pharmacol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1124\/dmd.110.033787","article-title":"Metabolism, excretion, and pharmacokinetics of [14C]INCB018424, a selective Janus tyrosine kinase 1\/2 inhibitor, in humans","volume":"38","author":"Shilling","year":"2010","journal-title":"Drug Metab. Dispos."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1056\/NEJMoa1409002","article-title":"Ruxolitinib versus standard therapy for the treatment of polycythemia vera","volume":"372","author":"Vannucchi","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"24006","DOI":"10.1038\/srep24006","article-title":"CADM1 inhibits squamous cell carcinoma progression by reducing STAT3 activity","volume":"6","author":"Vallath","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1245\/s10434-018-6532-4","article-title":"Circulating Interleukin-6 is Associated with Prognosis and Genetic Polymorphisms of MIR608 in Patients with Esophageal Squamous Cell Carcinoma","volume":"25","author":"Yang","year":"2018","journal-title":"Ann. Surg. Oncol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1016\/j.bbagen.2016.07.021","article-title":"JAK-mediated autophagy regulates stemness and cell survival in cisplatin resistant bladder cancer cells","volume":"1860","author":"Ojha","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Morgan, E.L., and Macdonald, A. (2019). JAK2 Inhibition Impairs Proliferation and Sensitises Cervical Cancer Cells to Cisplatin-Induced Cell Death. Cancers, 11.","DOI":"10.3390\/cancers11121934"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1155\/2010\/610974","article-title":"Activating mutation (V617F) in the tyrosine kinase JAK2 is absent in locally-confined or castration-resistant prostate cancer","volume":"33","author":"Gu","year":"2010","journal-title":"Anal. Cell Pathol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41375-020-0954-2","article-title":"Fedratinib, a newly approved treatment for patients with myeloproliferative neoplasm-associated myelofibrosis","volume":"35","author":"Talpaz","year":"2020","journal-title":"Leukemia"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.ccr.2008.02.009","article-title":"Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera","volume":"13","author":"Wernig","year":"2008","journal-title":"Cancer Cell"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.ccr.2010.05.015","article-title":"Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells","volume":"17","author":"Mullally","year":"2010","journal-title":"Cancer Cell"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ccr.2008.02.017","article-title":"Selective inhibition of JAK2-driven erythroid differentiation of polycythemia vera progenitors","volume":"13","author":"Geron","year":"2008","journal-title":"Cancer Cell"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1038\/leu.2008.56","article-title":"TG101348, a JAK2-selective antagonist, inhibits primary hematopoietic cells derived from myeloproliferative disorder patients with JAK2V617F, MPLW515K or JAK2 exon 12 mutations as well as mutation negative patients","volume":"22","author":"Lasho","year":"2008","journal-title":"Leukemia"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1200\/JCO.2010.32.8021","article-title":"Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis","volume":"29","author":"Pardanani","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1001\/jamaoncol.2015.1590","article-title":"Safety and Efficacy of Fedratinib in Patients With Primary or Secondary Myelofibrosis: A Randomized Clinical Trial","volume":"1","author":"Pardanani","year":"2015","journal-title":"JAMA Oncol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s00280-020-04067-3","article-title":"Effects of repeated oral doses of ketoconazole on a sequential ascending single oral dose of fedratinib in healthy subjects","volume":"85","author":"Ogasawara","year":"2020","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e317","DOI":"10.1016\/S2352-3026(17)30088-1","article-title":"Janus kinase-2 inhibitor fedratinib in patients with myelofibrosis previously treated with ruxolitinib (JAKARTA-2): A single-arm, open-label, non-randomised, phase 2, multicentre study","volume":"4","author":"Harrison","year":"2017","journal-title":"Lancet Haematol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"10777","DOI":"10.2147\/CMAR.S212559","article-title":"Beyond Ruxolitinib: Fedratinib and Other Emergent Treatment Options for Myelofibrosis","volume":"11","author":"Bewersdorf","year":"2019","journal-title":"Cancer Manag. Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1038\/leu.2011.148","article-title":"SB1518, a novel macrocyclic pyrimidine-based JAK2 inhibitor for the treatment of myeloid and lymphoid malignancies","volume":"25","author":"Hart","year":"2011","journal-title":"Leukemia"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"e44","DOI":"10.1038\/bcj.2011.43","article-title":"Pacritinib (SB1518), a JAK2\/FLT3 inhibitor for the treatment of acute myeloid leukemia","volume":"1","author":"Hart","year":"2011","journal-title":"Blood Cancer J."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"4638","DOI":"10.1021\/jm200326p","article-title":"Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[1 9.3.1.1(2,6). 1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2\/fms-like tyrosine kinase-3 (JAK2\/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma","volume":"54","author":"William","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1182\/blood-2013-02-484832","article-title":"Results of a phase 2 study of pacritinib (SB1518), a JAK2\/JAK2(V617F) inhibitor, in patients with myelofibrosis","volume":"125","author":"Komrokji","year":"2015","journal-title":"Blood"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1007\/s10637-019-00786-4","article-title":"Preclinical activity and a pilot phase I study of pacritinib, an oral JAK2\/FLT3 inhibitor, and chemotherapy in FLT3-ITD-positive AML","volume":"38","author":"Jeon","year":"2020","journal-title":"Investig. New Drugs"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.2217\/fon.15.200","article-title":"A comprehensive review of pacritinib in myelofibrosis","volume":"11","author":"Verstovsek","year":"2015","journal-title":"Future Oncol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1001\/jamaoncol.2017.5818","article-title":"Pacritinib vs Best Available Therapy, Including Ruxolitinib, in Patients with Myelofibrosis: A Randomized Clinical Trial","volume":"4","author":"Mascarenhas","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"28","DOI":"10.2174\/1872312809666150119105250","article-title":"Metabolism and Disposition of Pacritinib (SB1518), an Orally Active Janus Kinase 2 Inhibitor in Preclinical Species and Humans","volume":"9","author":"Jayaraman","year":"2015","journal-title":"Drug Metab. Lett."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Jensen, K.V., Cseh, O., Aman, A., Weiss, S., and Luchman, H.A. (2017). The JAK2\/STAT3 inhibitor pacritinib effectively inhibits patient-derived GBM brain tumor initiating cells in vitro and when used in combination with temozolomide increases survival in an orthotopic xenograft model. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0189670"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"5298","DOI":"10.4049\/jimmunol.0902819","article-title":"Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: Preclinical characterization of INCB028050","volume":"184","author":"Fridman","year":"2010","journal-title":"J. Immunol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"3568","DOI":"10.4049\/jimmunol.1201348","article-title":"Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases","volume":"191","author":"Galien","year":"2013","journal-title":"J. Immunol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1056\/NEJMoa1507247","article-title":"Baricitinib in Patients with Refractory Rheumatoid Arthritis","volume":"374","author":"Genovese","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1136\/annrheumdis-2019-216852","article-title":"Infections in baricitinib clinical trials for patients with active rheumatoid arthritis","volume":"79","author":"Winthrop","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1177\/1060028019839650","article-title":"Baricitinib: The Second FDA-Approved JAK Inhibitor for the Treatment of Rheumatoid Arthritis","volume":"53","author":"Mogul","year":"2019","journal-title":"Ann. Pharmacother."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/nrrheum.2017.51","article-title":"The emerging safety profile of JAK inhibitors in rheumatic disease","volume":"13","author":"Winthrop","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"e001370","DOI":"10.1136\/rmdopen-2020-001370","article-title":"Changes in selected haematological parameters associated with JAK1\/JAK2 inhibition observed in patients with rheumatoid arthritis treated with baricitinib","volume":"6","author":"Kay","year":"2020","journal-title":"RMD Open"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s40264-018-0651-5","article-title":"Thromboembolism with Janus Kinase (JAK) Inhibitors for Rheumatoid Arthritis: How Real is the Risk?","volume":"41","author":"Scott","year":"2018","journal-title":"Drug Saf."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1038\/leu.2009.50","article-title":"CYT387, a selective JAK1\/JAK2 inhibitor: In vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients","volume":"23","author":"Pardanani","year":"2009","journal-title":"Leukemia"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1038\/leu.2013.71","article-title":"Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis","volume":"27","author":"Pardanani","year":"2013","journal-title":"Leukemia"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3324\/haematol.2016.148924","article-title":"A phase 1\/2, open-label study evaluating twice-daily administration of momelotinib in myelofibrosis","volume":"102","author":"Gupta","year":"2017","journal-title":"Haematologica"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.leukres.2017.05.002","article-title":"A phase 2 study of momelotinib, a potent JAK1 and JAK2 inhibitor, in patients with polycythemia vera or essential thrombocythemia","volume":"60","author":"Verstovsek","year":"2017","journal-title":"Leuk. Res."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"3844","DOI":"10.1200\/JCO.2017.73.4418","article-title":"SIMPLIFY-1: A Phase III Randomized Trial of Momelotinib Versus Ruxolitinib in Janus Kinase Inhibitor-Naive Patients With Myelofibrosis","volume":"35","author":"Mesa","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.2217\/fon-2020-1048","article-title":"MOMENTUM: Momelotinib vs danazol in patients with myelofibrosis previously treated with JAKi who are symptomatic and anemic","volume":"17","author":"Verstovsek","year":"2021","journal-title":"Future Oncol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1016\/S2352-3026(17)30237-5","article-title":"Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): A randomised, open-label, phase 3 trial","volume":"5","author":"Harrison","year":"2018","journal-title":"Lancet Haematol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"e853","DOI":"10.1016\/j.cllc.2018.07.004","article-title":"Phase 1B Study of Momelotinib Combined With Trametinib in Metastatic, Kirsten Rat Sarcoma Viral Oncogene Homolog-Mutated Non-Small-Cell Lung Cancer After Platinum-Based Chemotherapy Treatment Failure","volume":"19","author":"Barbie","year":"2018","journal-title":"Clin. Lung Cancer"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.jtho.2020.11.007","article-title":"Combination of Immunotherapy and Antiangiogenic Therapy in Cancer-a Rational Approach","volume":"16","author":"Padda","year":"2021","journal-title":"J. Thorac. Oncol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"e109","DOI":"10.1038\/bcj.2013.6","article-title":"Discovery and characterization of LY2784544, a small-molecule tyrosine kinase inhibitor of JAK2V617F","volume":"3","author":"Ma","year":"2013","journal-title":"Blood Cancer J."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.leukres.2017.08.010","article-title":"A phase 1 study of the Janus kinase 2 (JAK2)(V617F) inhibitor, gandotinib (LY2784544), in patients with primary myelofibrosis, polycythemia vera, and essential thrombocythemia","volume":"61","author":"Verstovsek","year":"2017","journal-title":"Leuk. Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.leukres.2018.06.014","article-title":"Phase 2 study of gandotinib (LY2784544) in patients with myeloproliferative neoplasms","volume":"71","author":"Berdeja","year":"2018","journal-title":"Leuk. Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jphs.2016.12.001","article-title":"A novel JAK inhibitor, peficitinib, demonstrates potent efficacy in a rat adjuvant-induced arthritis model","volume":"133","author":"Ito","year":"2017","journal-title":"J. Pharmacol. Sci."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13075-020-2125-2","article-title":"Safety and effectiveness of peficitinib (ASP015K) in patients with rheumatoid arthritis: Interim data (22.7 months mean peficitinib treatment) from a long-term, open-label extension study in Japan, Korea, and Taiwan","volume":"22","author":"Takeuchi","year":"2020","journal-title":"Arthritis Res. Ther."},{"key":"ref_168","unstructured":"Astellas (2021, September 08). Oral JAK Inhibitor Smyraf\u00ae Tablets Approved in Japan for the Treatment of Rheumatoid Arthritis (Including Prevention of Structural Joint Damage) in Patients Who Have an Inadequate Response to Conventional Therapies. Available online: https:\/\/www.astellas.com\/system\/files\/news\/2019-03\/190326_eg_pefi_approval_final_0.pdf."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"3294","DOI":"10.1182\/blood-2010-08-301796","article-title":"Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse","volume":"117","author":"Levis","year":"2011","journal-title":"Blood"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.3109\/10428194.2014.1001986","article-title":"Phase I dose escalation study of lestaurtinib in patients with myelofibrosis","volume":"56","author":"Hexner","year":"2015","journal-title":"Leuk. Lymphoma"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.4161\/cbt.6.9.4541","article-title":"Preclinical and clinical studies with the multi-kinase inhibitor CEP-701 as treatment for prostate cancer demonstrate the inadequacy of PSA response as a primary endpoint","volume":"6","author":"Collins","year":"2007","journal-title":"Cancer Biol. Ther."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s40259-013-0040-7","article-title":"The arrival of JAK inhibitors: Advancing the treatment of immune and hematologic disorders","volume":"27","author":"Furumoto","year":"2013","journal-title":"BioDrugs"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"4234","DOI":"10.4049\/jimmunol.1003668","article-title":"Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550)","volume":"186","author":"Ghoreschi","year":"2011","journal-title":"J. Immunol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"6917","DOI":"10.1038\/s41598-019-43294-4","article-title":"Interleukin-7 Contributes to the Invasiveness of Prostate Cancer Cells by Promoting Epithelial-Mesenchymal Transition","volume":"9","author":"Seol","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1056\/NEJMoa1112168","article-title":"Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis","volume":"367","author":"Sandborn","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1158\/1078-0432.CCR-07-0524","article-title":"WP1066, a novel JAK2 inhibitor, suppresses proliferation and induces apoptosis in erythroid human cells carrying the JAK2 V617F mutation","volume":"14","author":"Verstovsek","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.3892\/or.2017.5902","article-title":"STAT3 inhibition by WP1066 suppresses the growth and invasiveness of bladder cancer cells","volume":"38","author":"Tsujita","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1038\/sj.bjc.6605691","article-title":"STAT3 inhibitor WP1066 as a novel therapeutic agent for renal cell carcinoma","volume":"102","author":"Horiguchi","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1021\/jm800984v","article-title":"Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity","volume":"52","author":"Howard","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1002\/ijc.26324","article-title":"AT9283, a novel aurora kinase inhibitor, suppresses tumor growth in aggressive B-cell lymphomas","volume":"130","author":"Qi","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_181","unstructured":"(2021, June 23). WP1066. (n.d.). Moleculin Biotech. Available online: https:\/\/www.moleculin.com\/technology\/wp1066\/."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1586\/era.09.14","article-title":"Prospect of JAK2 inhibitor therapy in myeloproliferative neoplasms","volume":"9","author":"Atallah","year":"2009","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_183","first-page":"329","article-title":"Atiprimod (AnorMED)","volume":"3","author":"Lakings","year":"2000","journal-title":"IDrugs"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1007\/s10637-010-9429-z","article-title":"Preclinical characterization of atiprimod, a novel JAK2 AND JAK3 inhibitor","volume":"29","author":"Manshouri","year":"2011","journal-title":"Investig. New Drugs"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1040a","DOI":"10.1182\/blood.V110.11.3556.3556","article-title":"Atiprimod inhibits the JAK-STAT pathway and induces apootosis in human cells carrying the JAK2(V617F) or JAK3 mutation","volume":"110","author":"Manshouri","year":"2007","journal-title":"Blood"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"5455","DOI":"10.1182\/blood-2006-12-063958","article-title":"Atiprimod inhibits the growth of mantle cell lymphoma in vitro and in vivo and induces apoptosis via activating the mitochondrial pathways","volume":"109","author":"Wang","year":"2007","journal-title":"Blood"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/sj.bjc.6602637","article-title":"Atiprimod blocks STAT3 phosphorylation and induces apoptosis in multiple myeloma cells","volume":"93","author":"Shishodia","year":"2005","journal-title":"Br. J. Cancer"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1177\/2040620711401646","article-title":"Update on JAK2 Inhibitors in Myeloproliferative Neoplasm","volume":"2","author":"Chan","year":"2011","journal-title":"Ther. Adv. Hematol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1182\/blood.V116.21.4107.4107","article-title":"Preferential Inhibition of An Activated Form of Janus Kinase 2 (JAK2) by a Novel JAK2 Inhibitor, NS-018","volume":"116","author":"Nakaya","year":"2010","journal-title":"Blood"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1182\/blood.V116.21.4106.4106","article-title":"NS-018, a Potent Novel JAK2 Inhibitor, Effectively Treats Murine MPN Induced by the Janus Kinase 2 (JAK2) V617F Mutant","volume":"116","author":"Shide","year":"2010","journal-title":"Blood"},{"key":"ref_191","unstructured":"Holladay, M.W., and Setti, E. (2014). Optically Active Pyrazolylaminoquinazoline, and Pharmaceutical Compositions and Methods of Use Thereof. (No. US8703943), US patent."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1158\/1535-7163.MCT-07-2215","article-title":"LS104, a non-ATP-competitive small-molecule inhibitor of JAK2, is potently inducing apoptosis in JAK2V617F-positive cells","volume":"7","author":"Lipka","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"604314","DOI":"10.3389\/fphar.2020.604314","article-title":"A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Multiple Ascending Dose and Food Effect Study to Evaluate the Tolerance, Pharmacokinetics of Jaktinib, a New Selective Janus Kinase Inhibitor in Healthy Chinese Volunteers, CLINICAL TRIAL","volume":"11","author":"Liu","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1158\/1078-0432.CCR-10-3012","article-title":"Antimyeloma activity of a multitargeted kinase inhibitor, AT9283, via potent Aurora kinase and STAT3 inhibition either alone or in combination with lenalidomide","volume":"17","author":"Santo","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.clml.2013.11.001","article-title":"A phase I and pharmacodynamic study of AT9283, a small-molecule inhibitor of aurora kinases in patients with relapsed\/refractory leukemia or myelofibrosis","volume":"14","author":"Foran","year":"2014","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"12953","DOI":"10.18632\/oncotarget.14588","article-title":"Dual SYK\/JAK inhibition overcomes ibrutinib resistance in chronic lymphocytic leukemia: Cerdulatinib, but not ibrutinib, induces apoptosis of tumor cells protected by the microenvironment","volume":"8","author":"Guo","year":"2017","journal-title":"Oncotarget"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1136\/annrheumdis-2020-219012","article-title":"JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib","volume":"80","author":"Traves","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1158\/1535-7163.MCT-17-0148","article-title":"JAK1\/STAT3 Activation through a Proinflammatory Cytokine Pathway Leads to Resistance to Molecularly Targeted Therapy in Non\u2013Small Cell Lung Cancer","volume":"16","author":"Shien","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1007\/s40265-020-01439-0","article-title":"Filgotinib: First Approval","volume":"80","author":"Dhillon","year":"2020","journal-title":"Drugs"},{"key":"ref_200","unstructured":"European Medicine Agency (2020, September 30). Filgotinib (Jyseleca\u00ae): Summary of product characteristics. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/jyseleca."},{"key":"ref_201","unstructured":"Eisai (2020, September 25). Jyseleca\u00ae (Filgotinib) Approved in Japan for Rheumatoid Arthritis [Press Release]. Available online: https:\/\/www.eisai.com\/news\/2020\/news202075.html."},{"key":"ref_202","unstructured":"Gilead Sciences Inc (2020, August 18). Gilead Receives Complete Response Letter for Filgotinib for the Treatment of Moderately to Severely Active Rheumatoid Arthritis [Press Release]. Available online: https:\/\/www.gilead.com\/news-and-press\/press-room\/press-releases\/2020\/8\/gilead-receives-complete-response-letter-for-filgotinib-for-the-treatment-of-moderately-to-severely-active-rheumatoid-arthritis."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1001\/jama.2019.9055","article-title":"Effect of Filgotinib vs Placebo on Clinical Response in Patients With Moderate to Severe Rheumatoid Arthritis Refractory to Disease-Modifying Antirheumatic Drug Therapy: The FINCH 2 Randomized Clinical Trial","volume":"322","author":"Genovese","year":"2019","journal-title":"JAMA"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1124\/jpet.114.221176","article-title":"VX-509 (decernotinib) is a potent and selective janus kinase 3 inhibitor that attenuates inflammation in animal models of autoimmune disease","volume":"353","author":"Mahajan","year":"2015","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/art.39473","article-title":"VX-509 (Decernotinib), an Oral Selective JAK-3 Inhibitor, in Combination With Methotrexate in Patients With Rheumatoid Arthritis","volume":"68","author":"Genovese","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"3428","DOI":"10.1074\/jbc.C600277200","article-title":"Erlotinib effectively inhibits JAK2V617F activity and polycythemia vera cell growth","volume":"282","author":"Li","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.urology.2009.05.016","article-title":"Erlotinib Has Moderate Single-agent Activity in Chemotherapy-na\u00efve Castration-resistant Prostate Cancer: Final Results of a Phase II Trial","volume":"74","author":"Nabhan","year":"2009","journal-title":"Urology"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s11010-019-03677-7","article-title":"Substance P receptor blocker, aprepitant, inhibited cutaneous and other neurogenic inflammation side effects of the EGFR1-TKI, erlotinib","volume":"465","author":"Chmielinska","year":"2020","journal-title":"Mol. Cell Biochem."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1111\/j.1365-2141.2010.08266.x","article-title":"A pilot study of the Histone-Deacetylase inhibitor Givinostat in patients with JAK2V617F positive chronic myeloproliferative neoplasms","volume":"150","author":"Rambaldi","year":"2010","journal-title":"Br. J. Haematol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1038\/leu.2017.93","article-title":"The histone deacetylase inhibitor givinostat (ITF2357) exhibits potent anti-tumor activity against CRLF2-rearranged BCP-ALL","volume":"31","author":"Savino","year":"2017","journal-title":"Leukemia"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1158\/1538-7445.AM2016-2132","article-title":"Abstract 2132: The novel, rationally-designed, ALK\/SRC inhibitor TPX-0005 overcomes multiple acquired resistance mechanisms to current ALK inhibitors","volume":"76","author":"Zhai","year":"2016","journal-title":"Cancer Res."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ebiom.2018.02.001","article-title":"Common Co-activation of AXL and CDCP1 in EGFR-mutation-positive Non-smallcell Lung Cancer Associated With Poor Prognosis","volume":"29","author":"Karachaliou","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1158\/2159-8290.CD-18-0484","article-title":"Repotrectinib (TPX-0005) Is a Next-Generation ROS1\/TRK\/ALK Inhibitor That Potently Inhibit ROS1\/TRK\/ALK Solvent-Front Mutations","volume":"8","author":"Drilon","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"3298","DOI":"10.1158\/1078-0432.CCR-20-4730","article-title":"Phase I Study of Zotiraciclib in Combination with Temozolomide for Patients with Recurrent High-grade Astrocytomas","volume":"27","author":"Wu","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1021\/jm201112g","article-title":"Discovery of kinase spectrum selective macrocycle (16E)-14-methyl-20-oxa-5,7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptaco sa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene (SB1317\/TG02), a potent inhibitor of cyclin dependent kinases (CDKs), Janus kinase 2 (JAK2), and fms-like tyrosine kinase-3 (FLT3) for the treatment of cancer","volume":"55","author":"William","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1158\/1535-7163.MCT-10-0053","article-title":"Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805","volume":"9","author":"Baffert","year":"2010","journal-title":"Mol. Cancer Ther."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"R68","DOI":"10.1186\/ar3329","article-title":"A highly selective, orally active inhibitor of Janus kinase 2, CEP-33779, ablates disease in two mouse models of rheumatoid arthritis","volume":"13","author":"Stump","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1158\/1535-7163.MCT-11-0951","article-title":"Therapeutic efficacy of CEP-33779, a novel selective JAK2 inhibitor, in a mouse model of colitis-induced colorectal cancer","volume":"11","author":"Seavey","year":"2012","journal-title":"Mol. Cancer Ther."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1038\/sj.leu.2404750","article-title":"TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L\/K mutations","volume":"21","author":"Pardanani","year":"2007","journal-title":"Leukemia"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"758a","DOI":"10.1182\/blood.V108.11.2680.2680","article-title":"TG101209, a selective JAK2 kinase inhibitor, suppresses endogenous and cytokine-supported colony formation from hematopoietic progenitors carrying JAK2V617F or MPLW515K\/L mutations","volume":"108","author":"Pardanani","year":"2006","journal-title":"Blood"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1097\/JTO.0b013e31820d9d11","article-title":"Inhibition of JAK2 signaling by TG101209 enhances radiotherapy in lung cancer models","volume":"6","author":"Sun","year":"2011","journal-title":"J. Thorac. Oncol."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"106753","DOI":"10.18632\/oncotarget.22053","article-title":"The effect of the JAK2 inhibitor TG101209 against T cell acute lymphoblastic leukemia (T-ALL) is mediated by inhibition of JAK-STAT signaling and activation of the crosstalk between apoptosis and autophagy signaling","volume":"8","author":"Cheng","year":"2017","journal-title":"Oncotarget"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1002\/ijc.25910","article-title":"Expression of p-JAK2 predicts clinical outcome and is a potential molecular target of acute myelogenous leukemia","volume":"129","author":"Ikezoe","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"32334","DOI":"10.1074\/jbc.M803813200","article-title":"Effects of the JAK2 inhibitor, AZ960, on Pim\/BAD\/BCL-xL survival signaling in the human JAK2 V617F cell line SET-2","volume":"283","author":"Gozgit","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1038\/nm1010-1085","article-title":"Peering into the aftermath: JAKi rips STAT3 in cancer","volume":"16","author":"Florian","year":"2010","journal-title":"Nat. Med."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1093\/jnci\/djr076","article-title":"Cancer burden in the HIV-infected population in the United States","volume":"103","author":"Shiels","year":"2011","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"eaat3834","DOI":"10.1126\/sciadv.aat3834","article-title":"Accumulation of JAK activation loop phosphorylation is linked to type I JAK inhibitor withdrawal syndrome in myelofibrosis","volume":"4","author":"Tvorogov","year":"2018","journal-title":"Sci. Adv."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1177\/1947601910371337","article-title":"A Non-ATP-Competitive Dual Inhibitor of JAK2 and BCR-ABL Kinases: Elucidation of a Novel Therapeutic Spectrum Based on Substrate Competitive Inhibition","volume":"1","author":"Jatiani","year":"2010","journal-title":"Genes Cancer"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1177\/1947601910372232","article-title":"Destabilization of Bcr-Abl\/Jak2 Network by a Jak2\/Abl Kinase Inhibitor ON044580 Overcomes Drug Resistance in Blast Crisis Chronic Myelogenous Leukemia (CML)","volume":"1","author":"Samanta","year":"2010","journal-title":"Genes Cancer"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13046-019-1062-x","article-title":"Discovery and evaluation of ZT55, a novel highly-selective tyrosine kinase inhibitor of JAK2V617F against myeloproliferative neoplasms","volume":"38","author":"Hu","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.ccr.2009.10.015","article-title":"The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors","volume":"16","author":"Hedvat","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/leu.2010.289","article-title":"The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting in suppression of human myeloma cell growth and survival","volume":"25","author":"Scuto","year":"2011","journal-title":"Leukemia"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"e46","DOI":"10.1038\/bcj.2011.46","article-title":"The JAK inhibitor AZD1480 regulates proliferation and immunity in Hodgkin lymphoma","volume":"1","author":"Derenzini","year":"2011","journal-title":"Blood Cancer J."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"7653","DOI":"10.1016\/j.bmcl.2012.10.007","article-title":"SAR and in vivo evaluation of 4-aryl-2-aminoalkylpyrimidines as potent and selective Janus kinase 2 (JAK2) inhibitors","volume":"22","author":"Forsyth","year":"2012","journal-title":"Bioorg Med. Chem. Lett."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.leukres.2013.12.006","article-title":"Phase I evaluation of XL019, an oral, potent, and selective JAK2 inhibitor","volume":"38","author":"Verstovsek","year":"2014","journal-title":"Leuk. Res."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1182\/blood.V122.21.664.664","article-title":"BMS-911543, A Selective JAK2 Inhibitor: A Multicenter Phase 1\/2a Study In Myelofibrosis","volume":"122","author":"Pardanani","year":"2013","journal-title":"Blood"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1021\/acsmedchemlett.5b00226","article-title":"Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms","volume":"6","author":"Wan","year":"2015","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/leu.2011.292","article-title":"Characterization of BMS-911543, a functionally selective small-molecule inhibitor of JAK2","volume":"26","author":"Purandare","year":"2012","journal-title":"Leukemia"},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41419-017-0245-7","article-title":"RIPK1-dependent cell death: A novel target of the Aurora kinase inhibitor Tozasertib (VX-680)","volume":"9","author":"Martens","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/nm1003","article-title":"VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo","volume":"10","author":"Harrington","year":"2004","journal-title":"Nat. Med."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1677\/ERC-08-0021","article-title":"Effects of the Aurora kinase inhibitor VX-680 on anaplastic thyroid cancer-derived cell lines","volume":"15","author":"Baldini","year":"2008","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1021\/jm101506n","article-title":"Crystal structures of ABL-related gene (ABL2) in complex with imatinib, tozasertib (VX-680), and a type I inhibitor of the triazole carbothioamide class","volume":"54","author":"Salah","year":"2011","journal-title":"J. Med. Chem."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/20\/5204\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:16:25Z","timestamp":1760166985000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/20\/5204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,17]]},"references-count":242,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["cancers13205204"],"URL":"https:\/\/doi.org\/10.3390\/cancers13205204","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,17]]}}}