{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T19:43:26Z","timestamp":1780429406470,"version":"3.54.1"},"reference-count":168,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T00:00:00Z","timestamp":1720569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Lorlatinib is a pharmaceutical ALK kinase inhibitor used to treat ALK driven non-small cell lung cancers. This paper analyses the intersection of past published data on the physiological consequences of two unrelated drugs from general medical practice\u2014itraconazole and cilostazol\u2014with the pathophysiology of ALK positive non-small cell lung cancer. A conclusion from that data analysis is that adding itraconazole and cilostazol may make lorlatinib more effective. Itraconazole, although marketed worldwide as a generic antifungal drug, also inhibits Hedgehog signaling, Wnt signaling, hepatic CYP3A4, and the p-gp efflux pump. Cilostazol, marketed worldwide as a generic thrombosis preventative drug, acts by inhibiting phosphodiesterase 3, and, by so doing, lowers platelets\u2019 adhesion, thereby partially depriving malignant cells of the many tumor trophic growth factors supplied by platelets. Itraconazole may enhance lorlatinib effectiveness by (i) reducing or stopping a Hedgehog-ALK amplifying feedback loop, by (ii) increasing lorlatinib\u2019s brain levels by p-gp inhibition, and by (iii) inhibiting growth drive from Wnt signaling. Cilostazol, surprisingly, carries minimal bleeding risk, lower than that of aspirin. Risk\/benefit assessment of the combination of metastatic ALK positive lung cancer being a low-survival disease with the predicted safety of itraconazole-cilostazol augmentation of lorlatinib favors a trial of this drug trio in ALK positive lung cancer.<\/jats:p>","DOI":"10.3390\/cells13141175","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T13:34:38Z","timestamp":1720618478000},"page":"1175","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["IC Regimen: Delaying Resistance to Lorlatinib in ALK Driven Cancers by Adding Repurposed Itraconazole and Cilostazol"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7876-0400","authenticated-orcid":false,"given":"Richard E.","family":"Kast","sequence":"first","affiliation":[{"name":"IIAIGC Study Center, Burlington, VT 05408, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,10]]},"reference":[{"key":"ref_1","first-page":"20","article-title":"ALK inhibitors in cancer: Mechanisms of resistance and therapeutic management strategies","volume":"7","author":"Poei","year":"2024","journal-title":"Cancer Drug Resist."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1080\/14737140.2024.2344648","article-title":"Navigating resistance to ALK inhibitors in the lorlatinib era: A comprehensive perspective on NSCLC","volume":"24","author":"Gemelli","year":"2024","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Fabbri, L., Di Federico, A., Astore, M., Marchiori, V., Rejtano, A., Seminerio, R., Gelsomino, F., and De Giglio, A. (2023). From Development to Place in Therapy of Lorlatinib for the Treatment of ALK and ROS1 Rearranged Non-Small Cell Lung Cancer (NSCLC). Diagnostics, 14.","DOI":"10.3390\/diagnostics14010048"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1038\/s41388-023-02712-8","article-title":"New perspectives for targeting therapy in ALK-positive human cancers","volume":"42","author":"Zhao","year":"2023","journal-title":"Oncogene"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/s43018-023-00515-0","article-title":"ALK-positive lung cancer: A moving target","volume":"4","author":"Schneider","year":"2023","journal-title":"Nat. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1002\/ijc.31582","article-title":"P-glycoprotein (MDR1\/ABCB1) restricts brain accumulation and cytochrome P450-3A (CYP3A) limits oral availability of the novel ALK\/ROS1 inhibitor lorlatinib","volume":"143","author":"Li","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.2217\/fon-2022-0184","article-title":"Lorlatinib as a treatment for ALK-positive lung cancer","volume":"18","author":"Baba","year":"2022","journal-title":"Future Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1634\/theoncologist.2018-0380","article-title":"Clinical Management of Adverse Events Associated with Lorlatinib","volume":"24","author":"Bauer","year":"2019","journal-title":"Oncologist"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.2217\/fon-2023-0014","article-title":"Safety of lorlatinib in ALK positive non-small-cell lung cancer and management of central nervous system adverse events","volume":"19","author":"Kilickap","year":"2023","journal-title":"Future Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1016\/j.ccell.2023.11.004","article-title":"ALK inhibitors increase ALK expression and sensitize neuroblastoma cells to ALK. CAR-T cells","volume":"41","author":"Bergaggio","year":"2023","journal-title":"Cancer Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e243","DOI":"10.1016\/j.jtho.2018.08.2025","article-title":"Identification of a High-Level MET Amplification in CTCs and cfTNA of an ALK-Positive NSCLC Patient Developing Evasive Resistance to Crizotinib","volume":"13","author":"Berger","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1080\/15384101.2016.1247568","article-title":"Resistance to ALK inhibitors: Pharmacokinetics, mutations or bypass signaling?","volume":"16","author":"Costa","year":"2017","journal-title":"Cell Cycle"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/s41571-022-00639-9","article-title":"Third-generation EGFR and ALK inhibitors: Mechanisms of resistance and management","volume":"19","author":"Cooper","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kast, R.E., Alfieri, A., Assi, H.I., Burns, T.C., Elyamany, A.M., Gonzalez-Cao, M., Karpel-Massler, G., Marosi, C., Salacz, M.E., and Sardi, I. (2022). MDACT: A New Principle of Adjunctive Cancer Treatment Using Combinations of Multiple Repurposed Drugs, with an Example Regimen. Cancers, 14.","DOI":"10.3390\/cancers14102563"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"vdab075","DOI":"10.1093\/noajnl\/vdab075","article-title":"A phase Ib\/IIa trial of 9 repurposed drugs combined with temozolomide for the treatment of recurrent glioblastoma: CUSP9v3","volume":"3","author":"Halatsch","year":"2021","journal-title":"Neuro-Oncol. Adv."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/s41586-021-04140-8","article-title":"Mechanism for the activation of the anaplastic lymphoma kinase receptor","volume":"600","author":"Reshetnyak","year":"2021","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Huang, H. (2018). Anaplastic Lymphoma Kinase (ALK) Receptor Tyrosine Kinase: A Catalytic Receptor with Many Faces. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113448"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Katic, L., and Priscan, A. (2023). Multifaceted Roles of ALK Family Receptors and Augmentor Ligands in Health and Disease: A Comprehensive Review. Biomolecules, 13.","DOI":"10.3390\/biom13101490"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.phrs.2012.11.007","article-title":"Anaplastic lymphoma kinase (ALK): Structure, oncogenic activation, and pharmacological inhibition","volume":"68","year":"2013","journal-title":"Pharmacol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Choo JR, Soo RA (2020). Lorlatinib for the treatment of ALK positive metastatic non-small cell lung cancer. Expert Rev. Anticancer Ther., 20, 233\u2013240.","DOI":"10.1080\/14737140.2020.1744438"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1200\/JCO.18.02236","article-title":"ALK Resistance Mutations and Efficacy of Lorlatinib in Advanced Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer","volume":"37","author":"Shaw","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5193","DOI":"10.1038\/onc.2012.12","article-title":"Anaplastic Lymphoma Kinase (ALK) regulates initiation of transcription of MYCN in neuroblastoma cells","volume":"31","author":"Ruuth","year":"2012","journal-title":"Oncogene"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3450","DOI":"10.1038\/srep03450","article-title":"ALK is a MYCN target gene and regulates cell migration and invasion in neuroblastoma","volume":"3","author":"Hasan","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s11864-010-0120-6","article-title":"Exciting new targets in lung cancer therapy: ALK, IGF-1R, HDAC, and Hh","volume":"11","author":"Neal","year":"2010","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.ctrv.2014.02.003","article-title":"Crosstalk between hedgehog and other signaling pathways as a basis for combination therapies in cancer","volume":"40","author":"Brechbiel","year":"2014","journal-title":"Cancer Treat. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Pite\u0161a, N., Kurtovi\u0107, M., Bartoni\u010dek, N., Gkotsi, D.S., \u010conka\u0161, J., Petri\u0107, T., Musani, V., Ozreti\u0107, P., Riobo-Del Galdo, N.A., and Sabol, M. (2023). Signaling Switching from Hedgehog-GLI to MAPK Signaling Potentially Serves as a Compensatory Mechanism in Melanoma Cell Lines Resistant to GANT-61. Biomedicines, 11.","DOI":"10.3390\/biomedicines11051353"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.semcancer.2015.08.003","article-title":"Mitogen-activated protein kinases and Hedgehog-GLI signaling in cancer: A crosstalk providing therapeutic opportunities?","volume":"35","author":"Rovida","year":"2015","journal-title":"Semin. Cancer Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.ajpath.2011.09.009","article-title":"Aberrant activation of the hedgehog signaling pathway in malignant hematological neoplasms","volume":"180","author":"Ok","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/B978-0-12-394622-5.00002-X","article-title":"Canonical and noncanonical Hedgehog\/GLI signaling in hematological malignancies","volume":"88","author":"Aberger","year":"2012","journal-title":"Vitam. Horm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8","DOI":"10.17305\/bjbms.2018.2756","article-title":"The role of the Hedgehog signaling pathway in cancer: A comprehensive review","volume":"18","author":"Skoda","year":"2018","journal-title":"Bosn. J. Basic. Med. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5895","DOI":"10.1073\/pnas.0700776104","article-title":"Melanomas require HEDGEHOG-GLI signaling regulated by interactions between GLI1 and the RAS-MEK\/AKT pathways","volume":"104","author":"Stecca","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Hwang, S.H., White, K.A., Somatilaka, B.N., Wang, B., and Mukhopadhyay, S. (2023). Context-dependent ciliary regulation of hedgehog pathway repression in tissue morphogenesis. PLoS Genet., 19.","DOI":"10.1371\/journal.pgen.1011028"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1158\/0008-5472.CAN-08-1808","article-title":"Sonic hedgehog signaling pathway is activated in ALK-positive anaplastic large cell lymphoma","volume":"69","author":"Singh","year":"2009","journal-title":"Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"150","DOI":"10.7150\/jca.46447","article-title":"ALKAL1 gene silencing prevents colorectal cancer progression via suppressing Sonic Hedgehog (SHH) signaling pathway","volume":"12","author":"Chen","year":"2021","journal-title":"J. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10335","DOI":"10.2147\/OTT.S270481","article-title":"Efficacy and Resistance of ALK Inhibitors in Two Inflammatory Myofibroblastic Tumor Patients with ALK Fusions Assessed by Whole Exome and RNA Sequencing","volume":"13","author":"Zhang","year":"2020","journal-title":"Onco. Targets Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.cellsig.2018.02.014","article-title":"Sonic hedgehog signaling pathway promotes INSM1 transcription factor in neuroendocrine lung cancer","volume":"46","author":"Chen","year":"2018","journal-title":"Cell Signal."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nature01493","article-title":"Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer","volume":"422","author":"Watkins","year":"2003","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1038\/nm.2473","article-title":"A crucial requirement for Hedgehog signaling in small cell lung cancer","volume":"17","author":"Park","year":"2011","journal-title":"Nat. Med."},{"key":"ref_39","first-page":"1148","article-title":"Inhibition of Gli leads to antitumor growth and enhancement of cisplatin-induced cytotoxicity in large cell neuroendocrine carcinoma of the lung","volume":"39","author":"Ishiwata","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ccr.2012.11.017","article-title":"Itraconazole and arsenic trioxide inhibit Hedgehog pathway activation and tumor growth associated with acquired resistance to smoothened antagonists","volume":"23","author":"Kim","year":"2013","journal-title":"Cancer Cell."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.canlet.2016.10.034","article-title":"Anti-proliferation of breast cancer cells with itraconazole: Hedgehog pathway inhibition induces apoptosis and autophagic cell death","volume":"385","author":"Wang","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13046-017-0526-0","article-title":"Itraconazole induces apoptosis and cell cycle arrest via inhibiting Hedgehog signaling in gastric cancer cells","volume":"36","author":"Hu","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"28510","DOI":"10.18632\/oncotarget.15324","article-title":"Itraconazole exerts its anti-melanoma effect by suppressing Hedgehog, Wnt, and PI3K\/mTOR signaling pathways","volume":"8","author":"Liang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.lfs.2018.12.012","article-title":"Triazoles bind the C-terminal domain of SMO: Illustration by docking and molecular dynamics simulations the binding between SMO and triazoles","volume":"217","author":"Liu","year":"2019","journal-title":"Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s11523-019-00648-2","article-title":"Hedgehog Pathway Inhibition for the Treatment of Basal Cell Carcinoma","volume":"14","author":"Gutzmer","year":"2019","journal-title":"Target. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Patel, S., Armbruster, H., Pardo, G., Archambeau, B., Kim, N.H., Jeter, J., Wu, R., Kendra, K., Contreras, C.M., and Spaccarelli, N. (2024). Hedgehog pathway inhibitors for locally advanced and metastatic basal cell carcinoma: A real-world single-center retrospective review. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0297531"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.18632\/oncotarget.1357","article-title":"Identification of anaplastic lymphoma kinase as a potential therapeutic target in Basal Cell Carcinoma","volume":"4","author":"Ning","year":"2013","journal-title":"Oncotarget"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4874","DOI":"10.1038\/onc.2011.195","article-title":"ABCG2 is a direct transcriptional target of hedgehog signaling and involved in stroma-induced drug tolerance in diffuse large B-cell lymphoma","volume":"30","author":"Singh","year":"2011","journal-title":"Oncogene"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6","DOI":"10.21037\/sci.2018.02.01","article-title":"Lung cancer stem cells-origin, characteristics and therapy","volume":"5","author":"Prabavathy","year":"2018","journal-title":"Stem. Cell Investig."},{"key":"ref_50","first-page":"187","article-title":"Clinical significance of cancer stem cell markers in lung carcinoma","volume":"68","author":"Zhang","year":"2021","journal-title":"Acta Biochim. Pol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.ejpb.2019.01.016","article-title":"Oral coadministration of elacridar and ritonavir enhances brain accumulation and oral availability of the novel ALK\/ROS1 inhibitor lorlatinib","volume":"136","author":"Li","year":"2019","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s10637-019-00872-7","article-title":"The effect of itraconazole on the pharmacokinetics of lorlatinib: Results of a phase I, open-label, crossover study in healthy participants","volume":"38","author":"Patel","year":"2020","journal-title":"Investig. New Drugs."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"173892","DOI":"10.1016\/j.ejphar.2021.173892","article-title":"Itraconazole synergistically increases therapeutic effect of paclitaxel and 99mTc-MIBI accumulation, as a probe of P-gp activity, in HT-29 tumor-bearing nude mice","volume":"895","author":"Ghadi","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1002\/alr.21454","article-title":"Itraconazole and clarithromycin inhibit P-glycoprotein activity in primary human sinonasal epithelial cells","volume":"5","author":"Lam","year":"2015","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3372","DOI":"10.1128\/AAC.02931-15","article-title":"Inhibitory Potential of Antifungal Drugs on ATP-Binding Cassette Transporters P-Glycoprotein, MRP1 to MRP5, BCRP, and BSEP","volume":"60","author":"Lempers","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1517\/14656566.1.2.287","article-title":"Itraconazole","volume":"1","author":"Arrese","year":"2000","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3226","DOI":"10.1002\/jps.20963","article-title":"Interactions of azole antifungal agents with the human breast cancer resistance protein (BCRP)","volume":"96","author":"Gupta","year":"2007","journal-title":"J. Pharm. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"115387","DOI":"10.1016\/j.taap.2020.115387","article-title":"Species-specific differences in the inhibition of 11\u03b2-hydroxysteroid dehydrogenase 2 by itraconazole and posaconazole","volume":"412","author":"Inderbinen","year":"2021","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"E7276","DOI":"10.1073\/pnas.1512867112","article-title":"Antifungal drug itraconazole targets VDAC1 to modulate the AMPK\/mTOR signaling axis in endothelial cells","volume":"112","author":"Head","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1021\/acschembio.6b00849","article-title":"Simultaneous Targeting of NPC1 and VDAC1 by Itraconazole Leads to Synergistic Inhibition of mTOR Signaling and Angiogenesis","volume":"12","author":"Head","year":"2017","journal-title":"ACS Chem. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1111\/cas.16082","article-title":"Itraconazole inhibits tumor growth via CEBPB-mediated glycolysis in colorectal cancer","volume":"115","author":"Zhang","year":"2024","journal-title":"Cancer Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1365-2249.2007.03470.x","article-title":"Itraconazole-mediated inhibition of calcium entry into platelet-activating factor-stimulated human neutrophils is due to interference with production of leukotriene B4","volume":"150","author":"Steel","year":"2007","journal-title":"Clin. Exp. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.3892\/ol.2017.6325","article-title":"Repurposing itraconazole as an anticancer agent","volume":"14","author":"Tsubamoto","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_64","first-page":"3521","article-title":"Itraconazole Modulates Hedgehog, WNT\/\u03b2-catenin, as well as Akt Signalling, and Inhibits Proliferation of Cervical Cancer Cells","volume":"37","author":"Ueda","year":"2017","journal-title":"Anticancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"9509","DOI":"10.12659\/MSM.919347","article-title":"Itraconazole Alters the Stem Cell Characteristics of A549 and NCI-H460 Human Lung Cancer Cells by Suppressing Wnt Signaling","volume":"25","author":"Chen","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Wang, W., Dong, X., Liu, Y., Ni, B., Sai, N., You, L., Sun, M., Yao, Y., Qu, C., and Yin, X. (2020). Itraconazole exerts anti-liver cancer potential through the Wnt, PI3K\/AKT\/mTOR, and ROS pathways. Biomed. Pharmacother., 131.","DOI":"10.1016\/j.biopha.2020.110661"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2004.08.040","article-title":"Wnt signaling in lung cancer","volume":"222","author":"Mazieres","year":"2005","journal-title":"Cancer Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1517\/14728222.2016.1154945","article-title":"Wnt signaling as potential therapeutic target in lung cancer","volume":"20","author":"Yang","year":"2016","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s12943-017-0700-1","article-title":"FOXP3 promotes tumor growth and metastasis by activating Wnt\/\u03b2-catenin signaling pathway and EMT in non-small cell lung cancer","volume":"16","author":"Yang","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s12943-021-01469-6","article-title":"LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway","volume":"20","author":"He","year":"2021","journal-title":"Mol. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s12032-021-01475-0","article-title":"The effect of itraconazole on the clinical outcomes of patients with advanced non-small cell lung cancer receiving platinum-based chemotherapy: A randomized controlled study","volume":"38","author":"Mohamed","year":"2021","journal-title":"Med. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6017","DOI":"10.1158\/1078-0432.CCR-20-1916","article-title":"Concentration-dependent Early Antivascular and Antitumor Effects of Itraconazole in Non-Small Cell Lung Cancer","volume":"26","author":"Gerber","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Halatsch, M.E., Dwucet, A., Schmidt, C.J., M\u00fchlnickel, J., Heiland, T., Zeiler, K., Siegelin, M.D., Kast, R.E., and Karpel-Massler, G. (2021). In Vitro and Clinical Compassionate Use Experiences with the Drug-Repurposing Approach CUSP9v3 in Glioblastoma. Pharmaceuticals, 14.","DOI":"10.3390\/ph14121241"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1634\/theoncologist.2012-314","article-title":"Repurposing itraconazole as a treatment for advanced prostate cancer: A noncomparative randomized phase II trial in men with metastatic castration-resistant prostate cancer","volume":"18","author":"Antonarakis","year":"2013","journal-title":"Oncologist"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e92","DOI":"10.1016\/j.clgc.2018.09.013","article-title":"Itraconazole as a Noncastrating Treatment for Biochemically Recurrent Prostate Cancer: A Phase 2 Study","volume":"17","author":"Lee","year":"2019","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1097\/JTO.0b013e31828c3950","article-title":"Phase 2 study of pemetrexed and itraconazole as second-line therapy for metastatic nonsquamous non-small-cell lung cancer","volume":"8","author":"Rudin","year":"2013","journal-title":"J. Thorac. Oncol."},{"key":"ref_77","first-page":"2481","article-title":"Impact of combination chemotherapy with itraconazole on survival of patients with refractory ovarian cancer","volume":"34","author":"Tsubamoto","year":"2014","journal-title":"Anticancer Res."},{"key":"ref_78","first-page":"2007","article-title":"Impact of combination chemotherapy with itraconazole on survival for patients with recurrent or persistent ovarian clear cell carcinoma","volume":"34","author":"Tsubamoto","year":"2014","journal-title":"Anticancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.2174\/1568026619666191122123855","article-title":"Progress in the Mechanism and Clinical Application of Cilostazol","volume":"19","author":"Zheng","year":"2019","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s10557-021-07187-x","article-title":"Cilostazol: A Review of Basic Mechanisms and Clinical Uses","volume":"36","author":"Kherallah","year":"2022","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"28D","DOI":"10.1016\/S0002-9149(01)01719-2","article-title":"Analysis of the cilostazol safety database","volume":"87","author":"Pratt","year":"2001","journal-title":"Am. J. Cardiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"89","DOI":"10.5758\/vsi.2017.33.3.89","article-title":"Cilostazol for Secondary Prevention of Stroke: Should the Guidelines Perhaps Be Extended?","volume":"33","author":"Galyfos","year":"2017","journal-title":"Vasc. Specialist Int."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"63","DOI":"10.2165\/00002512-199914010-00005","article-title":"Cilostazol","volume":"14","author":"Sorkin","year":"1999","journal-title":"Drugs Aging"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.1161\/STROKEAHA.120.029454","article-title":"Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis","volume":"51","author":"McHutchison","year":"2020","journal-title":"Stroke"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.atherosclerosissup.2005.09.002","article-title":"Cilostazol: Potential mechanism of action for antithrombotic effects accompanied by a low rate of bleeding","volume":"6","author":"Goto","year":"2005","journal-title":"Atheroscler. Suppl."},{"key":"ref_86","first-page":"S14","article-title":"The pharmacology of cilostazol","volume":"4","year":"2002","journal-title":"Diabetes Obes. Metab."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1161\/STROKEAHA.122.039900","article-title":"CSPS.com Trial Investigators. Dual Antiplatelet Therapy With Cilostazol for Secondary Prevention in Lacunar Stroke: Subanalysis of the CSPS. com Trial","volume":"54","author":"Nishiyama","year":"2023","journal-title":"Stroke"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1159\/000360811","article-title":"Benefit of cilostazol in patients with high risk of bleeding: Subanalysis of cilostazol stroke prevention study 2","volume":"37","author":"Uchiyama","year":"2014","journal-title":"Cerebrovasc. Dis."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Chai, E., Chen, J., Li, C., Zhang, X., Fan, Z., Yang, S., Zhao, K., Li, W., Xiao, Z., and Zhang, Y. (2022). The Efficacy and Safety of Cilostazol vs. Aspirin for Secondary Stroke Prevention: A Systematic Review and Meta-Analysis. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.814654"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.jstrokecerebrovasdis.2012.06.001","article-title":"Antiplatelet therapy as a risk factor for microbleeds in intracerebral hemorrhage patients: Analysis using specific antiplatelet agents","volume":"22","author":"Naka","year":"2013","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"105581","DOI":"10.1016\/j.jstrokecerebrovasdis.2020.105581","article-title":"Cilostazol Versus Aspirin for Secondary Stroke Prevention: Systematic Review and Meta-Analysis","volume":"30","author":"Lin","year":"2021","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_92","first-page":"269","article-title":"Comparison of the effects of acetylsalicylic acid, ticlopidine and cilostazol on primary hemostasis using a quantitative bleeding time test apparatus","volume":"29","author":"Tamai","year":"1999","journal-title":"Haemostasis"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.2174\/1381612033453910","article-title":"Cilostazol as a unique antithrombotic agent","volume":"9","author":"Kambayashi","year":"2003","journal-title":"Curr. Pharm. Des."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1002\/jcph.1988","article-title":"Update on Cilostazol: A Critical Review of Its Antithrombotic and Cardiovascular Actions and Its Clinical Applications","volume":"62","author":"Manolis","year":"2022","journal-title":"J. Clin. Pharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1527-3466.2001.tb00076.x","article-title":"Cilostazol (pletal): A dual inhibitor of cyclic nucleotide phosphodiesterase type 3 and adenosine uptake","volume":"19","author":"Liu","year":"2001","journal-title":"Cardiovasc. Drug Rev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1023\/A:1006626529536","article-title":"Phosphodiesterase type III inhibitor, cilostazol, inhibits colon cancer cell motility","volume":"17","author":"Murata","year":"1999","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1055\/s-0035-1564835","article-title":"Platelet Physiology","volume":"42","author":"Gremmel","year":"2016","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Beitia, M., Delgado, D., Mercader, J., S\u00e1nchez, P., L\u00f3pez de Dicastillo, L., and S\u00e1nchez, M. (2023). Action of Platelet-Rich Plasma on In Vitro Cellular Bioactivity: More than Platelets. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065367"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.cytogfr.2021.11.003","article-title":"Applications of the regenerative capacity of platelets in modern medicine","volume":"64","author":"Goszka","year":"2022","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"611","DOI":"10.3727\/0965040042707899","article-title":"Concentrations of VEGF and VEGFR1 in paired tumor arteries and veins in patients with rectal cancer","volume":"14","author":"Svendsen","year":"2004","journal-title":"Oncol. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1080\/00365510260296492","article-title":"Determination of vascular endothelial growth factor (VEGF) in circulating blood: Significance of VEGF in various leucocytes and platelets","volume":"62","author":"Werther","year":"2002","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1034\/j.1600-0463.2002.1100908.x","article-title":"VEGF concentrations in tumour arteries and veins from patients with rectal cancer","volume":"110","author":"Werther","year":"2002","journal-title":"APMIS"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Morris, K., Schnoor, B., and Papa, A.L. (2022). Platelet cancer cell interplay as a new therapeutic target. Biochim. Biophys. Acta Rev. Cancer, 1877.","DOI":"10.1016\/j.bbcan.2022.188770"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1158\/1078-0432.CCR-19-3906","article-title":"MET Alterations Are a Recurring and Actionable Resistance Mechanism in ALK-Positive Lung Cancer","volume":"26","author":"Yoda","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1186\/s40001-023-01342-w","article-title":"The critical role of platelet in cancer progression and metastasis","volume":"28","author":"Zhou","year":"2023","journal-title":"Eur. J. Med. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"S149","DOI":"10.1016\/S0049-3848(14)50025-4","article-title":"Mechanistic explanation for platelet contribution to cancer metastasis","volume":"133","author":"Stegner","year":"2014","journal-title":"Thromb. Res."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Wang, S., Li, Z., and Xu, R. (2018). Human Cancer and Platelet Interaction, a Potential Therapeutic Target. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041246"},{"key":"ref_108","first-page":"1146","article-title":"Platelet glycoprotein VI promotes metastasis through interaction with cancer cell-derived galectin-3","volume":"135","author":"Sarukhanyan","year":"2020","journal-title":"Blood"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1186\/s12967-024-05126-6","article-title":"The interaction of platelet-related factors with tumor cells promotes tumor metastasis","volume":"22","author":"Xue","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s10585-019-10009-y","article-title":"The contribution of platelets to intravascular arrest, extravasation, and outgrowth of disseminated tumor cells","volume":"37","author":"Foss","year":"2020","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1055\/s-0043-1776005","article-title":"Platelet Contributions to the (Pre)metastatic Tumor Microenvironment","volume":"50","author":"Roweth","year":"2024","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s13045-018-0669-2","article-title":"Role of platelets and platelet receptors in cancer metastasis","volume":"11","author":"Schlesinger","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.ejim.2013.01.017","article-title":"The platelet-cancer loop","volume":"24","author":"Goubran","year":"2013","journal-title":"Eur. J. Intern. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"45","DOI":"10.21037\/tlcr.2020.01.17","article-title":"Neutrophil or platelet-to-lymphocyte ratios in blood are associated with poor prognosis of pulmonary large cell neuroendocrine carcinoma","volume":"9","author":"Shi","year":"2020","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e25029","DOI":"10.1016\/j.heliyon.2024.e25029","article-title":"Prognostic scores in pulmonary large cell neuroendocrine carcinoma: A retrospective cohort study","volume":"10","author":"Akdag","year":"2024","journal-title":"Heliyon"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"51","DOI":"10.2217\/fon-2016-0317","article-title":"Platelet-lymphocyte ratio is an independent prognostic factor in patients with ALK-positive non small cell lung cancer","volume":"13","author":"Han","year":"2017","journal-title":"Future Oncol."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Andersen, B.L., Myers, J., Blevins, T., Park, K.R., Smith, R.M., Reisinger, S., Carbone, D.P., Presley, C.J., Shields, P.G., and Carson, W.E. (2023). Depression in association with neutrophil-to-lymphocyte, platelet-to-lymphocyte, and advanced lung cancer inflammation index biomarkers predicting lung cancer survival. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0282206"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"22618","DOI":"10.1038\/srep22618","article-title":"Prognostic value of platelet to lymphocyte ratio in non-small cell lung cancer: A systematic review and meta-analysis","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e22964","DOI":"10.1002\/jcla.22964","article-title":"Systemic immune inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio can predict clinical outcomes in patients with metastatic non-small-cell lung cancer treated with nivolumab","volume":"33","author":"Liu","year":"2019","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"e28617","DOI":"10.1097\/MD.0000000000028617","article-title":"The relationship between NLR\/PLR\/LMR levels and survival prognosis in patients with non-small cell lung carcinoma treated with immune checkpoint inhibitors","volume":"101","author":"Liu","year":"2022","journal-title":"Medicine"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1055\/s-0034-1370767","article-title":"Platelet-cancer interactions","volume":"40","author":"Goubran","year":"2014","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1038\/s41598-023-29450-x","article-title":"Prostate cancer cell-platelet bidirectional signaling promotes calcium mobilization, invasion and apoptotic resistance via distinct receptor ligand pairs","volume":"13","author":"Garofano","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"117690","DOI":"10.1016\/j.cca.2023.117690","article-title":"Tumor-educated platelets","volume":"552","author":"Najafi","year":"2024","journal-title":"Clin. Chim. Acta"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Coenen, D.M., Heinzmann, A.C.A., Oggero, S., Albers, H.J., Nagy, M., Hagu\u00e9, P., Kuijpers, M.J.E., Vanderwinden, J.M., van der Meer, A.D., and Perretti, M. (2021). JMEM. Inhibition of Phosphodiesterase 3A by Cilostazol Dampens Proinflammatory Platelet Functions. Cells, 10.","DOI":"10.3390\/cells10081998"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2010905","DOI":"10.1080\/2162402X.2021.2010905","article-title":"CCL5 production in lung cancer cells leads to an altered immune microenvironment and promotes tumor development","volume":"11","author":"Melese","year":"2021","journal-title":"Oncoimmunology"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2260625","DOI":"10.1155\/2022\/2260625","article-title":"Palbociclib Enhances Migration and Invasion of Cancer Cells via Senescence-Associated Secretory Phenotype-Related CCL5 in Non-Small-Cell Lung Cancer","volume":"2022","author":"Kong","year":"2022","journal-title":"J. Oncol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1002\/bab.1875","article-title":"EZH2 enhances expression of CCL5 to promote recruitment of macrophages and invasion in lung cancer","volume":"67","author":"Xia","year":"2020","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/s41419-020-2546-5","article-title":"Irradiation induces cancer lung metastasis through activation of the cGAS-STING-CCL5 pathway in mesenchymal stromal cells","volume":"11","author":"Zheng","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.bcp.2008.11.014","article-title":"CCL5 increases lung cancer migration via PI3K, Akt and NF-kappaB pathways","volume":"77","author":"Huang","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"474","DOI":"10.3109\/1354750X.2016.1172111","article-title":"CXC chemokine ligand 4 (CXCL4) is predictor of tumour angiogenic activity and prognostic biomarker in non-small cell lung cancer (NSCLC) patients undergoing surgical treatment","volume":"21","author":"Spaks","year":"2016","journal-title":"Biomarkers"},{"key":"ref_131","first-page":"6","article-title":"Whole Blood Analysis of Leukocyte Platelet Aggregates","volume":"78","author":"Gerrits","year":"2016","journal-title":"Curr. Protoc. Cytom."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1002\/ijc.33991","article-title":"Gene signature of circulating platelet-bound neutrophils is associated with poor prognosis in cancer patients","volume":"151","author":"Lecot","year":"2022","journal-title":"Int. J. Cancer"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Stoiber, D., and Assinger, A. (2020). Platelet-Leukocyte Interplay in Cancer Development and Progression. Cells, 9.","DOI":"10.3390\/cells9040855"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1053\/j.seminoncol.2014.04.003","article-title":"Platelets, selectins, and the control of tumor metastasis","volume":"41","author":"Coupland","year":"2014","journal-title":"Semin. Oncol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1055\/s-0037-1615217","article-title":"Effect of cilostazol on soluble adhesion molecules and platelet derived microparticles in patients with diabetes","volume":"80","author":"Nomura","year":"1998","journal-title":"Thromb. Haemost."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.ejvs.2008.11.028","article-title":"The effects of cilostazol on exercise-induced ischaemia reperfusion injury in patients with peripheral arterial disease","volume":"37","author":"Badger","year":"2009","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S0049-3848(00)00415-1","article-title":"Inhibition of platelet aggregation and the release of P-selectin from platelets by cilostazol","volume":"101","author":"Kariyazono","year":"2001","journal-title":"Thromb. Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.thromres.2020.09.021","article-title":"High plasma levels of soluble P-Selectin and Factor VIII predict venous thromboembolism in non-small cell lung cancer patients: The Thrombo-Nsclc risk score","volume":"196","author":"Segura","year":"2020","journal-title":"Thromb. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1067\/mcp.2003.13","article-title":"Clopidogrel but not aspirin reduces P-selectin expression and formation of platelet-leukocyte aggregates in patients with atherosclerotic vascular disease","volume":"73","author":"Klinkhardt","year":"2003","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1160\/TH06-08-0451","article-title":"Effect of antiplatelet agents clopidogrel, aspirin, and cilostazol on circulating tissue factor procoagulant activity in patients with peripheral arterial disease","volume":"96","author":"Rao","year":"2006","journal-title":"Thromb. Haemost."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"4446","DOI":"10.1182\/blood.V92.11.4446","article-title":"P-Selectin and platelet clearance","volume":"92","author":"Berger","year":"1998","journal-title":"Blood"},{"key":"ref_142","first-page":"147","article-title":"Platelet surface P-selectin molecules increased after exposing platelet to a high shear flow","volume":"19","author":"Goto","year":"2000","journal-title":"Int. Angiol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"11877","DOI":"10.1073\/pnas.93.21.11877","article-title":"In vivo tracking of platelets: Circulating degranulated platelets rapidly lose surface P-selectin but continue to circulate and function","volume":"93","author":"Michelson","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Fabricius, H.\u00c5., Starzonek, S., and Lange, T. (2021). The Role of Platelet Cell Surface P-Selectin for the Direct Platelet-Tumor Cell Contact During Metastasis Formation in Human Tumors. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.642761"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.2174\/0929867043364720","article-title":"P-selectin cell adhesion molecule in inflammation, thrombosis, cancer growth and metastasis","volume":"11","author":"Geng","year":"2004","journal-title":"Curr. Med. Chem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s00005-006-0010-6","article-title":"P-selectin mediates adhesion of leukocytes, platelets, and cancer cells in inflammation, thrombosis, and cancer growth and metastasis","volume":"54","author":"Chen","year":"2006","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.mvr.2004.05.002","article-title":"Cilostazol inhibits high glucose mediated endothelial neutrophil adhesion by decreasing adhesion molecule expression via NO production","volume":"68","author":"Omi","year":"2004","journal-title":"Microvasc. Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"56B","DOI":"10.1016\/S0828-282X(06)70987-4","article-title":"The vascular effects of cilostazol","volume":"22","author":"Weintraub","year":"2006","journal-title":"Can. J. Cardiol."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Sohn, M., and Lim, S. (2024). The Role of Cilostazol, a Phosphodiesterase-3 Inhibitor, in the Development of Atherosclerosis and Vascular Biology: A Review with Meta-Analysis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052593"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.atherosclerosis.2011.09.048","article-title":"Effect of cilostazol on the progression of carotid intima media thickness: A meta-analysis of randomized controlled trials","volume":"220","author":"Geng","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1097\/FJC.0000000000001195","article-title":"Efficacy and Safety of Cilostazol for Atherosclerosis: A Meta-analysis of Randomized Controlled Trials","volume":"79","author":"Wan","year":"2022","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1097\/00006676-200408000-00008","article-title":"The influence of platelets on the promotion of invasion by tumor cells and inhibition by antiplatelet agents","volume":"29","author":"Suzuki","year":"2004","journal-title":"Pancreas"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"113147","DOI":"10.1016\/j.celrep.2023.113147","article-title":"Cancer cells reprogram to metastatic state through the acquisition of platelet mitochondria","volume":"42","author":"Zhang","year":"2023","journal-title":"Cell Rep."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Cereceda, L., Cardenas, J.C., Khoury, M., Silva-Pavez, E., and Hidalgo, Y. (2024). Impact of platelet-derived mitochondria transfer in the metabolic profiling and progression of metastatic MDA-MB-231 human triple-negative breast cancer cells. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1324158"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1158\/1541-7786.MCR-23-0329","article-title":"Mitochondria Transfer by Platelet-Derived Microparticles Regulates Breast Cancer Bioenergetic States and Malignant Features","volume":"22","author":"Veilleux","year":"2024","journal-title":"Mol. Cancer Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s13046-024-03069-w","article-title":"Mitochondrial transfer in tunneling nanotubes-a new target for cancer therapy","volume":"43","author":"Guan","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2151996","DOI":"10.1080\/09537104.2022.2151996","article-title":"Platelet-derived mitochondria transfer facilitates wound closure by modulating ROS levels in dermal fibroblasts","volume":"34","author":"Kim","year":"2022","journal-title":"Platelets"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1080\/09537104.2021.1961717","article-title":"Platelet-derived respiratory competent mitochondria transfer to mesenchymal stem cells to promote wound healing via metabolic reprogramming","volume":"33","author":"Chen","year":"2022","journal-title":"Platelets"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.cmet.2020.12.006","article-title":"Platelets Facilitate the Wound-Healing Capability of Mesenchymal Stem Cells by Mitochondrial Transfer and Metabolic Reprogramming","volume":"33","author":"Levoux","year":"2021","journal-title":"Cell Metab."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1634\/theoncologist.2016-0488","article-title":"ALK Fusions in a Wide Variety of Tumor Types Respond to Anti-ALK Targeted Therapy","volume":"22","author":"Ross","year":"2017","journal-title":"Oncologist"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41698-023-00449-x","article-title":"ALK fusions in the pan-cancer setting: Another tumor-agnostic target?","volume":"7","author":"Shreenivas","year":"2023","journal-title":"NPJ Precis. Oncol."},{"key":"ref_162","first-page":"1079","article-title":"Inhibition of experimental metastasis of human adenocarcinoma by cilostazol, a platelet phosphodiesterase inhibitor","volume":"2","author":"Inufusa","year":"1995","journal-title":"Oncol. Rep."},{"key":"ref_163","first-page":"1148","article-title":"Cilostazol eliminates radiation-resistant glioblastoma by re-evoking big conductance calcium-activated potassium channel activity","volume":"11","author":"Liu","year":"2021","journal-title":"Am. J. Cancer Res."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Naderbar, L., Pazhang, Y., and Rezaie, J. (2022). Inhibiting AKT signaling pathway with cilostazol and meloxicam synergism for suppressing K562 cells in vitro. J. Biochem. Mol. Toxicol., 36.","DOI":"10.1002\/jbt.23185"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1158\/1535-7163.MCT-18-1233","article-title":"Phosphodiesterase 3A Represents a Therapeutic Target that Drives Stem Cell-like Property and Metastasis in Breast Cancer","volume":"19","author":"Hao","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.18632\/oncotarget.26734","article-title":"Potentiation of imatinib by cilostazol in sensitive and resistant gastrointestinal stromal tumor cell lines involves YAP inhibition","volume":"10","author":"Vandenberghe","year":"2019","journal-title":"Oncotarget"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/cam4.56","article-title":"Targeting phosphodiesterase 3B enhances cisplatin sensitivity in human cancer cells","volume":"2","author":"Uzawa","year":"2013","journal-title":"Cancer Med."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s10585-009-9299-y","article-title":"Inhibition of metastasis in a murine 4T1 breast cancer model by liposomes preventing tumor cell-platelet interactions","volume":"27","author":"Wenzel","year":"2010","journal-title":"Clin. Exp. Metastasis"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/14\/1175\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:12:43Z","timestamp":1760109163000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/14\/1175"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,10]]},"references-count":168,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["cells13141175"],"URL":"https:\/\/doi.org\/10.3390\/cells13141175","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,10]]}}}