{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T19:36:55Z","timestamp":1784230615441,"version":"3.55.0"},"reference-count":149,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"City of Hope Comprehensive Cancer Center Biomarker Core","doi-asserted-by":"publisher","award":["T32CA221709"],"award-info":[{"award-number":["T32CA221709"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"City of Hope Comprehensive Cancer Center Biomarker Core","doi-asserted-by":"publisher","award":["CA220693"],"award-info":[{"award-number":["CA220693"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"City of Hope Comprehensive Cancer Center Biomarker Core","doi-asserted-by":"publisher","award":["CA24619"],"award-info":[{"award-number":["CA24619"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Triple-negative breast cancer (TNBC) surpasses other BC subtypes as the most challenging to treat due to its lack of traditional BC biomarkers. Nearly 30% of TNBC patients express the androgen receptor (AR), and the blockade of androgen production and AR signaling have been the cornerstones of therapies for AR-positive TNBC. However, the majority of women are resistant to AR-targeted therapy, which is a major impediment to improving outcomes for the AR-positive TNBC subpopulation. The hypoxia signaling cascade is frequently activated in the tumor microenvironment in response to low oxygen levels; activation of the hypoxia signaling cascade allows tumors to survive despite hypoxia-mediated interference with cellular metabolism. The activation of hypoxia signaling networks in TNBC promotes resistance to most anticancer drugs including AR inhibitors. The activation of hypoxia network signaling occurs more frequently in TNBC compared to other BC subtypes. Herein, we examine the (1) interplay between hypoxia signaling networks and AR and (2) whether hypoxia and hypoxic stress adaptive pathways promote the emergence of resistance to therapies that target AR. We also pose the well-supported question, \u201cCan the efficacy of androgen-\/AR-targeted treatments be enhanced by co-targeting hypoxia?\u201d By critically examining the evidence and the complex entwinement of these two oncogenic pathways, we argue that the simultaneous targeting of androgen biosynthesis\/AR signaling and hypoxia may enhance the sensitivity of AR-positive TNBCs to AR-targeted treatments, derail the emergence of therapy resistance, and improve patient outcomes.<\/jats:p>","DOI":"10.3390\/ijms23168844","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T02:42:53Z","timestamp":1660099373000},"page":"8844","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Adaptation to Hypoxia May Promote Therapeutic Resistance to Androgen Receptor Inhibition in Triple-Negative Breast Cancer"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4068-2881","authenticated-orcid":false,"given":"Nikita","family":"Jinna","sequence":"first","affiliation":[{"name":"Department of Population Science, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padmashree","family":"Rida","sequence":"additional","affiliation":[{"name":"Rowland Hall, Salt Lake City, UT 84102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Smart","sequence":"additional","affiliation":[{"name":"Rowland Hall, Salt Lake City, UT 84102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"LaBarge","sequence":"additional","affiliation":[{"name":"Department of Population Science, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1928-4763","authenticated-orcid":false,"given":"Tijana","family":"Jovanovic-Talisman","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4494-1788","authenticated-orcid":false,"given":"Rama","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Department of Diabetes Complications and Metabolism, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Seewaldt","sequence":"additional","affiliation":[{"name":"Department of Population Science, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1200\/JCO.2013.50.9984","article-title":"American Society of Clinical O, College of American P: Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology\/College of American Pathologists clinical practice guideline update","volume":"31","author":"Wolff","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4429","DOI":"10.1158\/1078-0432.CCR-06-3045","article-title":"Triple-negative breast cancer: Clinical features and patterns of recurrence","volume":"13","author":"Dent","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2638","DOI":"10.1002\/cncr.23930","article-title":"Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: High incidence of central nervous system metastases","volume":"113","author":"Lin","year":"2008","journal-title":"Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.bulcan.2019.12.012","article-title":"Androgen receptor-positive triple negative breast cancer: From biology to therapy","volume":"107","author":"Grellety","year":"2020","journal-title":"Bull. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1158\/1535-7163.MCT-14-0926","article-title":"Multiple molecular subtypes of triple-negative breast cancer critically rely on androgen receptor and respond to enzalutamide in vivo","volume":"14","author":"Barton","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5505","DOI":"10.1158\/1078-0432.CCR-12-3327","article-title":"Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer","volume":"19","author":"Gucalp","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1093\/annonc\/mdw067","article-title":"A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1)","volume":"27","author":"Bonnefoi","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1200\/JCO.2016.71.3495","article-title":"Enzalutamide for the Treatment of Androgen Receptor-Expressing Triple-Negative Breast Cancer","volume":"36","author":"Traina","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s12943-018-0869-y","article-title":"Role of hypoxia-induced exosomes in tumor biology","volume":"17","author":"Shao","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_10","first-page":"4693","article-title":"Overexpression of hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer","volume":"60","author":"Birner","year":"2000","journal-title":"Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.pharmthera.2016.04.009","article-title":"Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer","volume":"164","author":"Wigerup","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4214","DOI":"10.1038\/s41388-018-0259-3","article-title":"Intermittent hypoxia induces a metastatic phenotype in breast cancer","volume":"37","author":"Chen","year":"2018","journal-title":"Oncogene"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/nrc3064","article-title":"Targeting hypoxia in cancer therapy","volume":"11","author":"Wilson","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5769","DOI":"10.1158\/1078-0432.CCR-17-0874","article-title":"Bevacizumab Induces Acute Hypoxia and Cancer Progression in Patients with Refractory Breast Cancer: Multimodal Functional Imaging and Multiplex Cytokine Analysis","volume":"23","author":"Ueda","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s12943-019-1089-9","article-title":"Role of hypoxia in cancer therapy by regulating the tumor microenvironment","volume":"18","author":"Jing","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/nrc1187","article-title":"Targeting HIF-1 for cancer therapy","volume":"3","author":"Semenza","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7658","DOI":"10.1158\/1078-0432.CCR-05-0460","article-title":"The androgen receptor is significantly associated with vascular endothelial growth factor and hypoxia sensing via hypoxia-inducible factors HIF-1a, HIF-2a, and the prolyl hydroxylases in human prostate cancer","volume":"11","author":"Boddy","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4304","DOI":"10.1073\/pnas.90.9.4304","article-title":"General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia","volume":"90","author":"Wang","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jsbmb.2010.10.009","article-title":"Hypoxia enhances transcriptional activity of androgen receptor through hypoxia-inducible factor-1alpha in a low androgen environment","volume":"123","author":"Mitani","year":"2011","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"108497","DOI":"10.1016\/j.steroids.2019.108497","article-title":"Hypoxia induced cancer stem cell enrichment promotes resistance to androgen deprivation therapy in prostate cancer","volume":"152","author":"Johnson","year":"2019","journal-title":"Steroids"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5121","DOI":"10.1158\/0008-5472.CAN-05-1341","article-title":"Hypoxia increases androgen receptor activity in prostate cancer cells","volume":"66","author":"Park","year":"2006","journal-title":"Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4972","DOI":"10.1038\/s41467-018-07411-7","article-title":"Interplay between hypoxia and androgen controls a metabolic switch conferring resistance to androgen\/AR-targeted therapy","volume":"9","author":"Geng","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Tran, M.G.B., Bibby, B.A.S., Yang, L., Lo, F., Warren, A.Y., Shukla, D., Osborne, M., Hadfield, J., Carroll, T., and Stark, R. (2020). Independence of HIF1a and androgen signaling pathways in prostate cancer. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-06890-6"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.urolonc.2011.12.007","article-title":"Chronic hypoxia induces androgen-independent and invasive behavior in LNCaP human prostate cancer cells","volume":"31","author":"Yamasaki","year":"2013","journal-title":"Urol. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1124\/mol.114.097477","article-title":"Dual targeting of the androgen receptor and hypoxia-inducible factor 1alpha pathways synergistically inhibits castration-resistant prostate cancer cells","volume":"87","author":"Fernandez","year":"2015","journal-title":"Mol. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3177\/jnsv.60.276","article-title":"Resveratrol inhibits hypoxia-inducible factor-1alpha-mediated androgen receptor signaling and represses tumor progression in castration-resistant prostate cancer","volume":"60","author":"Mitani","year":"2014","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s12951-021-00786-8","article-title":"Targeting triple-negative breast cancer with an aptamer-functionalized nanoformulation: A synergistic treatment that combines photodynamic and bioreductive therapies","volume":"19","author":"Chou","year":"2021","journal-title":"J. Nanobiotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jsbmb.2012.08.007","article-title":"Androgen receptor in triple negative breast cancer","volume":"133","author":"McNamara","year":"2013","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4105","DOI":"10.1021\/bi102059z","article-title":"Mechanism of androgen receptor antagonism by bicalutamide in the treatment of prostate cancer","volume":"50","author":"Osguthorpe","year":"2011","journal-title":"Biochemistry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0090-4295(96)00117-3","article-title":"Agonist and antagonist activities of hydroxyflutamide and Casodex relate to androgen receptor stabilization","volume":"48","author":"Kemppainen","year":"1996","journal-title":"Urology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1056\/NEJMoa1207506","article-title":"Increased survival with enzalutamide in prostate cancer after chemotherapy","volume":"367","author":"Scher","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1158\/0008-5472.CAN-11-3948","article-title":"ARN-509: A novel antiandrogen for prostate cancer treatment","volume":"72","author":"Clegg","year":"2012","journal-title":"Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1586\/14737140.2015.1081566","article-title":"ODM-201: A new-generation androgen receptor inhibitor in castration-resistant prostate cancer","volume":"15","author":"Fizazi","year":"2015","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1634\/theoncologist.2016-0240","article-title":"Metastatic Breast Cancer With ESR1 Mutation: Clinical Management Considerations From the Molecular and Precision Medicine (MAP) Tumor Board at Massachusetts General Hospital","volume":"21","author":"Bardia","year":"2016","journal-title":"Oncologist"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.currproblcancer.2016.09.004","article-title":"Targeting the androgen receptor in triple-negative breast cancer","volume":"40","author":"Gucalp","year":"2016","journal-title":"Curr. Probl. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3389\/fendo.2020.00035","article-title":"Seviteronel, a Novel CYP17 Lyase Inhibitor and Androgen Receptor Antagonist, Radiosensitizes AR-Positive Triple Negative Breast Cancer Cells","volume":"11","author":"Michmerhuizen","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"R77","DOI":"10.1186\/bcr2419","article-title":"PD 0332991, a selective cyclin D kinase 4\/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro","volume":"11","author":"Finn","year":"2009","journal-title":"Breast Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3994","DOI":"10.1038\/sj.onc.1209415","article-title":"An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen","volume":"25","author":"Doane","year":"2006","journal-title":"Oncogene"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s10549-010-1012-y","article-title":"Clinicopathologic and molecular significance of phospho-Akt expression in early invasive breast cancer","volume":"127","author":"Aleskandarany","year":"2011","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1172\/JCI45014","article-title":"Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies","volume":"121","author":"Lehmann","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1158\/1078-0432.CCR-19-2170","article-title":"TBCRC 032 IB\/II Multicenter Study: Molecular Insights to AR Antagonist and PI3K Inhibitor Efficacy in Patients with AR(+) Metastatic Triple-Negative Breast Cancer","volume":"26","author":"Lehmann","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6276","DOI":"10.1038\/s41467-021-26502-6","article-title":"Multi-omics analysis identifies therapeutic vulnerabilities in triple-negative breast cancer subtypes","volume":"12","author":"Lehmann","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11511","DOI":"10.1096\/fj.201903167R","article-title":"Unique targeting of androgen-dependent and -independent AR signaling in prostate cancer to overcome androgen resistance","volume":"34","author":"Lim","year":"2020","journal-title":"FASEB J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1158\/1541-7786.MCR-21-0780","article-title":"Attenuating Adaptive VEGF-A and IL8 Signaling Restores Durable Tumor Control in AR Antagonist-Treated Prostate Cancers","volume":"20","author":"Maxwell","year":"2022","journal-title":"Mol. Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.bbrc.2012.01.019","article-title":"Hypoxia enhances ligand-occupied androgen receptor activity","volume":"418","author":"Park","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_46","first-page":"2416","article-title":"Androgens stimulate hypoxia-inducible factor 1 activation via autocrine loop of tyrosine kinase receptor\/phosphatidylinositol 3\u2019-kinase\/protein kinase B in prostate cancer cells","volume":"9","author":"Mabjeesh","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1158\/1541-7786.MCR-06-0226","article-title":"Androgen-dependent gene expression of prostate-specific antigen is enhanced synergistically by hypoxia in human prostate cancer cells","volume":"5","author":"Horii","year":"2007","journal-title":"Mol. Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"33594","DOI":"10.1074\/jbc.M112.388298","article-title":"Coordinated action of hypoxia-inducible factor-1alpha and beta-catenin in androgen receptor signaling","volume":"287","author":"Mitani","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_49","first-page":"6724810","article-title":"Suppression of TRPM7 Inhibited Hypoxia-Induced Migration and Invasion of Androgen-Independent Prostate Cancer Cells by Enhancing RACK1-Mediated Degradation of HIF-1alpha","volume":"2020","author":"Yang","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.18632\/oncotarget.2841","article-title":"A switch from CD44(+) cell to EMT cell drives the metastasis of prostate cancer","volume":"6","author":"Shang","year":"2015","journal-title":"Oncotarget"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s10585-009-9242-2","article-title":"Invasive prostate cancer cells are tumor initiating cells that have a stem cell-like genomic signature","volume":"26","author":"Klarmann","year":"2009","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1182\/blood-2016-10-745588","article-title":"Targeting chronic myeloid leukemia stem cells with the hypoxia-inducible factor inhibitor acriflavine","volume":"130","author":"Cheloni","year":"2017","journal-title":"Blood"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ma, Y., Liang, D., Liu, J., Axcrona, K., Kvalheim, G., Stokke, T., Nesland, J.M., and Suo, Z. (2011). Prostate cancer cell lines under hypoxia exhibit greater stem-like properties. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0029170"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1158\/1541-7786.MCR-14-0153-T","article-title":"HIF1alpha Regulates mTOR Signaling and Viability of Prostate Cancer Stem Cells","volume":"13","author":"Marhold","year":"2015","journal-title":"Mol. Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Krishnamachary, B., Penet, M.F., Nimmagadda, S., Mironchik, Y., Raman, V., Solaiyappan, M., Semenza, G.L., Pomper, M.G., and Bhujwalla, Z.M. (2012). Hypoxia regulates CD44 and its variant isoforms through HIF-1alpha in triple negative breast cancer. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044078"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas (2012). Comprehensive molecular portraits of human breast tumours. Nature, 490, 61\u201370.","DOI":"10.1038\/nature11412"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.neo.2022.01.003","article-title":"Targeting hypoxia regulated sodium driven bicarbonate transporters reduces triple negative breast cancer metastasis","volume":"25","author":"Carroll","year":"2022","journal-title":"Neoplasia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/jcp.25411","article-title":"Low-Dose Farnesyltransferase Inhibitor Suppresses HIF-1alpha and Snail Expression in Triple-Negative Breast Cancer MDA-MB-231 Cells In Vitro","volume":"232","author":"Tanaka","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"15326","DOI":"10.18632\/oncotarget.24569","article-title":"Metabolic consequences of HIF silencing in a triple negative human breast cancer xenograft","volume":"9","author":"Bharti","year":"2018","journal-title":"Oncotarget"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"607142","DOI":"10.3389\/fcell.2021.607142","article-title":"Hypoxia-Mediated Complement 1q Binding Protein Regulates Metastasis and Chemoresistance in Triple-Negative Breast Cancer and Modulates the PKC-NF-kappaB-VCAM-1 Signaling Pathway","volume":"9","author":"Wu","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Sarnella, A., D\u2019Avino, G., Hill, B.S., Alterio, V., Winum, J.Y., Supuran, C.T., De Simone, G., and Zannetti, A. (2020). A Novel Inhibitor of Carbonic Anhydrases Prevents Hypoxia-Induced TNBC Cell Plasticity. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218405"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Cheng, F.Y., Chan, C.H., Wang, B.J., Yeh, Y.L., Wang, Y.J., and Chiu, H.W. (2021). The Oxygen-Generating Calcium Peroxide-Modified Magnetic Nanoparticles Attenuate Hypoxia-Induced Chemoresistance in Triple-Negative Breast Cancer. Cancers, 13.","DOI":"10.3390\/cancers13040606"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Godet, I., Mamo, M., Thurnheer, A., Rosen, D.M., and Gilkes, D.M. (2021). Post-Hypoxic Cells Promote Metastatic Recurrence after Chemotherapy Treatment in TNBC. Cancers, 13.","DOI":"10.3390\/cancers13215509"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Sulaiman, A., McGarry, S., Chambers, J., Al-Kadi, E., Phan, A., Li, L., Mediratta, K., Dimitroulakos, J., Addison, C., and Li, X. (2020). Targeting Hypoxia Sensitizes TNBC to Cisplatin and Promotes Inhibition of Both Bulk and Cancer Stem Cells. Int. J. Mol. Sci., 21.","DOI":"10.20944\/preprints202007.0527.v1"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1038\/s41467-020-16199-4","article-title":"Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer","volume":"11","author":"Saatci","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e17370","DOI":"10.1097\/MD.0000000000017370","article-title":"Prediction of postoperative survival of triple-negative breast cancer based on nomogram model combined with expression of HIF-1alpha and c-myc","volume":"98","author":"Cui","year":"2019","journal-title":"Medicine"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"700062","DOI":"10.3389\/fonc.2021.700062","article-title":"Identification of a Hypoxia-Related Molecular Classification and Hypoxic Tumor Microenvironment Signature for Predicting the Prognosis of Patients with Triple-Negative Breast Cancer","volume":"11","author":"Sun","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"19486","DOI":"10.18632\/aging.203360","article-title":"A combined hypoxia and immune gene signature for predicting survival and risk stratification in triple-negative breast cancer","volume":"13","author":"Yang","year":"2021","journal-title":"Aging"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/sj.bjc.6603295","article-title":"Expression of oestrogen receptor-beta in oestrogen receptor-alpha negative human breast tumours","volume":"95","author":"Skliris","year":"2006","journal-title":"Br. J. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/modpathol.2009.158","article-title":"Estrogen receptor-beta expression in invasive breast cancer in relation to molecular phenotype: Results from the Nurses\u2019 Health Study","volume":"23","author":"Marotti","year":"2010","journal-title":"Mod. Pathol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"R21","DOI":"10.1186\/bcr3619","article-title":"Estrogen receptor beta as a novel target of androgen receptor action in breast cancer cell lines","volume":"16","author":"Rizza","year":"2014","journal-title":"Breast Cancer Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3727","DOI":"10.1200\/JCO.2007.14.2968","article-title":"Clinical importance of estrogen receptor-beta evaluation in breast cancer patients treated with adjuvant tamoxifen therapy","volume":"26","author":"Honma","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"R32","DOI":"10.1186\/bcr2854","article-title":"Estrogen receptor beta inhibits transcriptional activity of hypoxia inducible factor-1 through the downregulation of arylhydrocarbon receptor nuclear translocator","volume":"13","author":"Lim","year":"2011","journal-title":"Breast Cancer Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.ctrv.2015.04.009","article-title":"Is androgen receptor targeting an emerging treatment strategy for triple negative breast cancer?","volume":"41","author":"Anestis","year":"2015","journal-title":"Cancer Treat. Rev."},{"key":"ref_75","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_76","doi-asserted-by":"crossref","first-page":"33384","DOI":"10.1074\/jbc.M302581200","article-title":"Role of the glucocorticoid receptor for regulation of hypoxia-dependent gene expression","volume":"278","author":"Kodama","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.4049\/jimmunol.174.4.2250","article-title":"Potentiation of glucocorticoid activity in hypoxia through induction of the glucocorticoid receptor","volume":"174","author":"Leonard","year":"2005","journal-title":"J. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/nature11125","article-title":"The mutational landscape of lethal castration-resistant prostate cancer","volume":"487","author":"Grasso","year":"2012","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/ng.2301","article-title":"Traversing the genomic landscape of prostate cancer from diagnosis to death","volume":"44","author":"Hieronymus","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.cell.2015.06.053","article-title":"Integrative Clinical Genomics of Advanced Prostate Cancer","volume":"162","author":"Robinson","year":"2015","journal-title":"Cell"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1158\/0008-5472.CAN-17-3006","article-title":"Inhibition of the Wnt\/beta-Catenin Pathway Overcomes Resistance to Enzalutamide in Castration-Resistant Prostate Cancer","volume":"78","author":"Zhang","year":"2018","journal-title":"Cancer Res."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Lee, E., Ha, S., and Logan, S.K. (2015). Divergent Androgen Receptor and Beta-Catenin Signaling in Prostate Cancer Cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0141589"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ccr.2011.05.026","article-title":"Targeting androgen receptor in estrogen receptor-negative breast cancer","volume":"20","author":"Ni","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.7150\/thno.36182","article-title":"Response to mTOR and PI3K inhibitors in enzalutamide-resistant luminal androgen receptor triple-negative breast cancer patient-derived xenografts","volume":"10","author":"Coussy","year":"2020","journal-title":"Theranostics"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"7200","DOI":"10.1073\/pnas.121173298","article-title":"Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor","volume":"98","author":"Lin","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Crumbaker, M., Khoja, L., and Joshua, A.M. (2017). AR Signaling and the PI3K Pathway in Prostate Cancer. Cancers, 9.","DOI":"10.3390\/cancers9040034"},{"key":"ref_87","first-page":"11","article-title":"PI3K-AKT-mTOR pathway is dominant over androgen receptor signaling in prostate cancer cells","volume":"32","author":"Kaarbo","year":"2010","journal-title":"Cell Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.3892\/ijo.2014.2601","article-title":"Targeting the PI3K\/Akt pathway in prostate cancer: Challenges and opportunities (review)","volume":"45","author":"Toren","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41585-021-00438-4","article-title":"Resistance to second-generation androgen receptor antagonists in prostate cancer","volume":"18","author":"Schmidt","year":"2021","journal-title":"Nat. Rev. Urol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"755","DOI":"10.3892\/or.2016.4903","article-title":"Phosphorylated mTOR is associated to androgen receptor expression in early triple-negative breast cancer","volume":"36","author":"Pistelli","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Brumec, M., Sobocan, M., Takac, I., and Arko, D. (2021). Clinical Implications of Androgen-Positive Triple-Negative Breast Cancer. Cancers, 13.","DOI":"10.3390\/cancers13071642"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"10765","DOI":"10.1038\/s41598-021-90143-4","article-title":"Abiraterone induces SLCO1B3 expression in prostate cancer via microRNA-579-3p","volume":"11","author":"Barbier","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1016\/j.ejca.2012.12.003","article-title":"An in vivo hypoxia metagene identifies the novel hypoxia inducible factor target gene SLCO1B3","volume":"49","author":"Ramachandran","year":"2013","journal-title":"Eur. J. Cancer"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.3892\/or.2014.3322","article-title":"Aberrant expression of enhancer of zeste homologue 2, correlated with HIF-1alpha, refines relapse risk and predicts poor outcome for breast cancer","volume":"32","author":"Dong","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/tbj.12238","article-title":"Correlation between HIF-1alpha expression and breast cancer risk: A meta-analysis","volume":"20","author":"Sun","year":"2014","journal-title":"Breast J."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"789414","DOI":"10.1155\/2015\/789414","article-title":"Interleukin-1beta Affects MDAMB231 Breast Cancer Cell Migration under Hypoxia: Role of HIF-1alpha and NFkappaB Transcription Factors","volume":"2015","author":"Filippi","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"28329","DOI":"10.1038\/srep28329","article-title":"EMMPRIN Down-regulating miR-106a\/b Modifies Breast Cancer Stem-like Cell Properties via Interaction with Fibroblasts Through STAT3 and HIF-1alpha","volume":"6","author":"Liu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s13402-017-0335-7","article-title":"MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR\/HIF-1alpha\/VEGF signaling axis in breast cancer cells","volume":"40","author":"Pakravan","year":"2017","journal-title":"Cell Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1158\/1078-0432.CCR-17-3571","article-title":"Targeting Bromodomain and Extra-Terminal (BET) Family Proteins in Castration-Resistant Prostate Cancer (CRPC)","volume":"24","author":"Welti","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/onc.2016.184","article-title":"The BET inhibitor JQ1 selectively impairs tumour response to hypoxia and downregulates CA9 and angiogenesis in triple negative breast cancer","volume":"36","author":"Ledaki","year":"2017","journal-title":"Oncogene"},{"key":"ref_101","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_102","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1158\/0008-5472.CAN-08-2764","article-title":"Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer","volume":"69","author":"Hu","year":"2009","journal-title":"Cancer Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1158\/0008-5472.CAN-08-3795","article-title":"A novel androgen receptor splice variant is up-regulated during prostate cancer progression and promotes androgen depletion-resistant growth","volume":"69","author":"Guo","year":"2009","journal-title":"Cancer Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1172\/JCI41824","article-title":"Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant","volume":"120","author":"Sun","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Hornberg, E., Ylitalo, E.B., Crnalic, S., Antti, H., Stattin, P., Widmark, A., Bergh, A., and Wikstrom, P. (2011). Expression of androgen receptor splice variants in prostate cancer bone metastases is associated with castration-resistance and short survival. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019059"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1158\/0008-5472.CAN-10-1998","article-title":"Intragenic rearrangement and altered RNA splicing of the androgen receptor in a cell-based model of prostate cancer progression","volume":"71","author":"Li","year":"2011","journal-title":"Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"16759","DOI":"10.1073\/pnas.1012443107","article-title":"Constitutively active androgen receptor splice variants expressed in castration-resistant prostate cancer require full-length androgen receptor","volume":"107","author":"Watson","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_108","first-page":"2234","article-title":"Resistance to androgen-pathway drugs in prostate cancer","volume":"371","author":"Antonarakis","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1097\/JU.0000000000001568","article-title":"Efficacy of Enzalutamide plus Androgen Deprivation Therapy in Metastatic Hormone-Sensitive Prostate Cancer by Pattern of Metastatic Spread: ARCHES Post Hoc Analyses","volume":"205","author":"Armstrong","year":"2021","journal-title":"J. Urol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/s41419-020-02932-w","article-title":"The miR-361-3p increases enzalutamide (Enz) sensitivity via targeting the ARv7 and MKNK2 to better suppress the Enz-resistant prostate cancer","volume":"11","author":"Liu","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1530\/EC-19-0340","article-title":"AR mRNA stability is increased with AR-antagonist resistance via 3\u2032UTR variants","volume":"9","author":"Dart","year":"2020","journal-title":"Endocr. Connect."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41388-021-02103-x","article-title":"Targeting KDM4A-AS1 represses AR\/AR-Vs deubiquitination and enhances enzalutamide response in CRPC","volume":"41","author":"Zhang","year":"2022","journal-title":"Oncogene"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/s41419-021-04449-2","article-title":"HIF-1alpha-activated long non-coding RNA KDM4A-AS1 promotes hepatocellular carcinoma progression via the miR-411-5p\/KPNA2\/AKT pathway","volume":"12","author":"Chen","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e2585","DOI":"10.1038\/cddis.2016.477","article-title":"Proteasome-associated deubiquitinase ubiquitin-specific protease 14 regulates prostate cancer proliferation by deubiquitinating and stabilizing androgen receptor","volume":"8","author":"Liao","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s12672-014-0171-4","article-title":"Identification of androgen receptor splice variant transcripts in breast cancer cell lines and human tissues","volume":"5","author":"Hu","year":"2014","journal-title":"Horm. Cancer"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"44728","DOI":"10.18632\/oncotarget.6296","article-title":"Expression of androgen receptor splice variants in clinical breast cancers","volume":"6","author":"Hickey","year":"2015","journal-title":"Oncotarget"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1016\/j.biopha.2016.10.076","article-title":"Nimbolide inhibits androgen independent prostate cancer cells survival and proliferation by modulating multiple pro-survival signaling pathways","volume":"84","author":"Singh","year":"2016","journal-title":"Biomed. Pharm."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s13046-020-01616-9","article-title":"Hypoxia-induced alternative splicing: The 11th Hallmark of Cancer","volume":"39","author":"Farina","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1002\/med.21663","article-title":"Spotlighting the hypoxia-centrosome amplification axis","volume":"40","author":"Mittal","year":"2020","journal-title":"Med. Res. Rev."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Mittal, K., Choi, D.H., Wei, G., Kaur, J., Klimov, S., Arora, K., Griffith, C.C., Kumar, M., Imhansi-Jacob, P., and Melton, B.D. (2020). Hypoxia-Induced Centrosome Amplification Underlies Aggressive Disease Course in HPV-Negative Oropharyngeal Squamous Cell Carcinomas. Cancers, 12.","DOI":"10.3390\/cancers12020517"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1158\/1541-7786.MCR-20-0798","article-title":"Hypoxia Drives Centrosome Amplification in Cancer Cells via HIF1alpha-dependent Induction of Polo-Like Kinase 4","volume":"20","author":"Mittal","year":"2022","journal-title":"Mol. Cancer Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3667","DOI":"10.1091\/mbc.e08-01-0042","article-title":"Transcriptional regulation of serine\/threonine kinase-15 (STK15) expression by hypoxia and HIF-1","volume":"19","author":"Klein","year":"2008","journal-title":"Mol. Biol. Cell."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.mam.2015.05.001","article-title":"Turning the headlights on novel cancer biomarkers: Inspection of mechanics underlying intratumor heterogeneity","volume":"45","author":"McBride","year":"2015","journal-title":"Mol. Asp. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s10555-012-9413-5","article-title":"Heading off with the herd: How cancer cells might maneuver supernumerary centrosomes for directional migration","volume":"32","author":"Ogden","year":"2013","journal-title":"Cancer Metastasis Rev."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/s41598-017-00363-w","article-title":"Prognostic value of CA20, a score based on centrosome amplification-associated genes, in breast tumors","volume":"7","author":"Ogden","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"de Almeida, B.P., Vieira, A.F., Paredes, J., Bettencourt-Dias, M., and Barbosa-Morais, N.L. (2019). Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome. PLoS Comput. Biol., 15.","DOI":"10.1371\/journal.pcbi.1006832"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1002\/path.2860","article-title":"Overexpression of miR-210, a downstream target of HIF1alpha, causes centrosome amplification in renal carcinoma cells","volume":"224","author":"Nakada","year":"2011","journal-title":"J. Pathol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"10487","DOI":"10.18632\/oncotarget.3402","article-title":"Rampant centrosome amplification underlies more aggressive disease course of triple negative breast cancers","volume":"6","author":"Pannu","year":"2015","journal-title":"Oncotarget"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1038\/cdd.2012.61","article-title":"Let\u2019s huddle to prevent a muddle: Centrosome declustering as an attractive anticancer strategy","volume":"19","author":"Ogden","year":"2012","journal-title":"Cell Death Differ."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Woo, Y.M., Shin, Y., Lee, E.J., Lee, S., Jeong, S.H., Kong, H.K., Park, E.Y., Kim, H.K., Han, J., and Chang, M. (2015). Inhibition of Aerobic Glycolysis Represses Akt\/mTOR\/HIF-1alpha Axis and Restores Tamoxifen Sensitivity in Antiestrogen-Resistant Breast Cancer Cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132285"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Yehia, L., Boulos, F., Jabbour, M., Mahfoud, Z., Fakhruddin, N., and El-Sabban, M. (2015). Expression of HIF-1alpha and Markers of Angiogenesis Are Not Significantly Different in Triple Negative Breast Cancer Compared to Other Breast Cancer Molecular Subtypes: Implications for Future Therapy. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129356"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"R15","DOI":"10.1186\/bcr3609","article-title":"Nonhypoxic regulation and role of hypoxia-inducible factor 1 in aromatase inhibitor resistant breast cancer","volume":"16","author":"Kazi","year":"2014","journal-title":"Breast Cancer Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"10151","DOI":"10.7314\/APJCP.2014.15.23.10151","article-title":"4-Hydroxynonenal promotes growth and angiogenesis of breast cancer cells through HIF-1alpha stabilization","volume":"15","author":"Li","year":"2014","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12943-019-0954-x","article-title":"Targeting PI3K in cancer: Mechanisms and advances in clinical trials","volume":"18","author":"Yang","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1182\/blood-2015-04-639138","article-title":"MAPK signaling cascades mediate distinct glucocorticoid resistance mechanisms in pediatric leukemia","volume":"126","author":"Jones","year":"2015","journal-title":"Blood"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.ccr.2013.10.022","article-title":"Direct reversal of glucocorticoid resistance by AKT inhibition in acute lymphoblastic leukemia","volume":"24","author":"Piovan","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1038\/leu.2017.136","article-title":"JAK\/STAT pathway inhibition overcomes IL7-induced glucocorticoid resistance in a subset of human T-cell acute lymphoblastic leukemias","volume":"31","author":"Meyer","year":"2017","journal-title":"Leukemia"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nm.1900","article-title":"Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia","volume":"15","author":"Real","year":"2009","journal-title":"Nat. Med."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s13045-020-00990-3","article-title":"Targeting the Wnt\/beta-catenin signaling pathway in cancer","volume":"13","author":"Zhang","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3349\/ymj.2017.58.3.489","article-title":"Development of Inhibitors Targeting Hypoxia-Inducible Factor 1 and 2 for Cancer Therapy","volume":"58","author":"Yu","year":"2017","journal-title":"Yonsei Med. J."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"719836","DOI":"10.3389\/fonc.2021.719836","article-title":"Vascular Normalization: A New Window Opened for Cancer Therapies","volume":"11","author":"Yang","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1093\/jnci\/94.12.883","article-title":"Clinical application of antiangiogenic therapy: Microvessel density, what it does and doesn\u2019t tell us","volume":"94","author":"Hlatky","year":"2002","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1126\/science.1104819","article-title":"Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy","volume":"307","author":"Jain","year":"2005","journal-title":"Science"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1200\/JCO.2012.46.3653","article-title":"Normalizing tumor microenvironment to treat cancer: Bench to bedside to biomarkers","volume":"31","author":"Jain","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1126\/science.1125950","article-title":"Antiangiogenic therapy: A universal chemosensitization strategy for cancer?","volume":"312","author":"Kerbel","year":"2006","journal-title":"Science"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"881551","DOI":"10.3389\/fmed.2022.881551","article-title":"Non-conventional and Investigational PET Radiotracers for Breast Cancer: A Systematic Review","volume":"9","author":"Balma","year":"2022","journal-title":"Front. Med. (Lausanne)"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.molonc.2015.12.011","article-title":"Monitoring vascular normalization induced by antiangiogenic treatment with (18)F-fluoromisonidazole-PET","volume":"10","author":"Mondejar","year":"2016","journal-title":"Mol. Oncol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1097\/RLU.0000000000000286","article-title":"Head and neck tumor hypoxia imaging by 18F-fluoroazomycin-arabinoside (18F-FAZA)-PET: A review","volume":"39","author":"Halmos","year":"2014","journal-title":"Clin. Nucl. Med."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Kersemans, V., Cornelissen, B., Hueting, R., Tredwell, M., Hussien, K., Allen, P.D., Falzone, N., Hill, S.A., Dilworth, J.R., and Gouverneur, V. (2011). Hypoxia imaging using PET and SPECT: The effects of anesthetic and carrier gas on [Cu]-ATSM, [Tc]-HL91 and [F]-FMISO tumor hypoxia accumulation. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025911"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/16\/8844\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:06:07Z","timestamp":1760141167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/16\/8844"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,9]]},"references-count":149,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23168844"],"URL":"https:\/\/doi.org\/10.3390\/ijms23168844","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,9]]}}}