From fungus fighter to cancer slayer: itraconazole as a multifaceted candidate for drug-resistant prostate cancer

Barsouk A, Padala SA, Vakiti A, Mohammed A, Saginala K, Thandra KC, et al. Epidemiology, staging and management of prostate cancer. Med Sci. 2020;8:3.

Article  Google Scholar 

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229–63.

PubMed  Google Scholar 

Denmeade SR, Isaacs JT. A history of prostate cancer treatment. Nat Rev Cancer. 2002;2:389–96.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J Clin. 1972;22:232–40.

CAS  PubMed  Google Scholar 

Chakrabarti D, Albertsen P, Adkins A, Kishan A, Murthy V, Parker C, et al. The contemporary management of prostate cancer. CA Cancer J Clin. 2025;75:552–86.

PubMed  PubMed Central  Google Scholar 

Sharifi N, Gulley JL, Dahut WL. Androgen deprivation therapy for prostate cancer. JAMA. 2005;294:238–44.

Article  CAS  PubMed  Google Scholar 

Litwin MS, Tan HJ. The diagnosis and treatment of prostate cancer: a review. JAMA. 2017;317:2532–42.

Article  PubMed  Google Scholar 

Karantanos T, Corn PG, Thompson TC. Prostate cancer progression after androgen deprivation therapy: mechanisms of castrate resistance and novel therapeutic approaches. Oncogene. 2013;32:5501–11.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cai M, Song XL, Li XA, Chen M, Guo J, Yang DH, et al. Current therapy and drug resistance in metastatic castration-resistant prostate cancer. Drug Resist Updat. 2023;68:100962.

Article  CAS  PubMed  Google Scholar 

Gillessen S, Turco F, Davis ID, Efstathiou JA, Fizazi K, James ND, et al. Management of patients with advanced prostate cancer. Report from the 2024 advanced prostate cancer consensus conference (APCCC). Eur Urol. 2025;87:157–216.

Article  PubMed  Google Scholar 

Park JC, Eisenberger MA. Advances in the treatment of metastatic prostate cancer. Mayo Clin Proc. 2015;90:1719–33.

Article  CAS  PubMed  Google Scholar 

Komura K, Sweeney CJ, Inamoto T, Ibuki N, Azuma H, Kantoff PW. Current treatment strategies for advanced prostate cancer. Int J Urol. 2018;25:220–31.

Article  PubMed  Google Scholar 

Abida W, Cyrta J, Heller G, Prandi D, Armenia J, Coleman I, et al. Genomic correlates of clinical outcome in advanced prostate cancer. Proc Natl Acad Sci USA. 2019;116:11428–36.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lima TS, Iglesias-Gato D, Souza LDO, Stenvang J, Lima DS, Roder MA, et al. Molecular profiling of docetaxel-resistant prostate cancer cells identifies multiple mechanisms of therapeutic resistance. Cancers. 2021;13:1290.

Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015;161:1215–28.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Seguier D, Parent P, Duterque-Coquillaud M, Labreuche J, Fromont-Hankard G, Dariane C, et al. Emergence of neuroendocrine tumors in patients treated with androgen receptor pathway inhibitors for metastatic prostate cancer: a systematic review and meta-analysis. Eur Urol Oncol. 2025;8:581–90.

Article  PubMed  Google Scholar 

Khorasanchi A, Hong F, Yang Y, Singer EA, Wang P, Li M, et al. Overcoming drug resistance in castrate-resistant prostate cancer: current mechanisms and emerging therapeutic approaches. Cancer Drug Resist. 2025;8:9.

CAS  PubMed  PubMed Central  Google Scholar 

Stenvang J, Kumler I, Nygard SB, Smith DH, Nielsen D, Brunner N, et al. Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy: a novel strategy in drug development. Front Oncol. 2013;3:313.

Article  PubMed  PubMed Central  Google Scholar 

Mohi-Ud-Din R, Chawla A, Sharma P, Mir PA, Potoo FH, Reiner Z, et al. Repurposing approved non-oncology drugs for cancer therapy: a comprehensive review of mechanisms, efficacy, and clinical prospects. Eur J Med Res. 2023;28:345.

Article  PubMed  PubMed Central  Google Scholar 

Pantziarka P, Sukhatme V, Bouche G, Meheus L, Sukhatme VP. Repurposing Drugs in Oncology (ReDO)-itraconazole as an anti-cancer agent. Ecancermedicalscience. 2015;9:521.

Article  PubMed  PubMed Central  Google Scholar 

Zonfa CE, Thyagarajan A, Sahu RP. Repurposing itraconazole in combination with chemotherapy and immune checkpoint inhibitor for cancer. Med Sci. 2026;14:55.

Fromtling RA. Overview of medically important antifungal azole derivatives. Clin Microbiol Rev. 1988;1:187–217.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Patel V, Liaw B, Oh W. The role of ketoconazole in current prostate cancer care. Nat Rev Urol. 2018;15:643–51.

Article  CAS  PubMed  Google Scholar 

Antonarakis ES, Heath EI, Smith DC, Rathkopf D, Blackford AL, Danila DC, et al. Repurposing itraconazole as a treatment for advanced prostate cancer: a noncomparative randomized phase II trial in men with metastatic castration-resistant prostate cancer. Oncologist. 2013;18:163–73.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Suzman DL, Antonarakis ES. High-dose itraconazole as a noncastrating therapy for a patient with biochemically recurrent prostate cancer. Clin Genitourin Cancer. 2014;12:e51–3.

Article  PubMed  Google Scholar 

Lima TS, Souza LO, Iglesias-Gato D, Elversang J, Jorgensen FS, Kallunki T, et al. Itraconazole reverts ABCB1-mediated docetaxel resistance in prostate cancer. Front Pharmacol. 2022;13:869461.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim J, Tang JY, Gong R, Kim J, Lee JJ, Clemons KV, et al. Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth. Cancer Cell. 2010;17:388–99.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pace JR, DeBerardinis AM, Sail V, Tacheva-Grigorova SK, Chan KA, Tran R, et al. Repurposing the clinically efficacious antifungal agent itraconazole as an anticancer chemotherapeutic. J Med Chem. 2016;59:3635–49.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tsubamoto H, Ueda T, Inoue K, Sakata K, Shibahara H, Sonoda T. Repurposing itraconazole as an anticancer agent. Oncol Lett. 2017;14:1240–6.

Article  PubMed  PubMed Central  Google Scholar 

Takara K, Tanigawara Y, Komada F, Nishiguchi K, Sakaeda T, Okumura K. Cellular pharmacokinetic aspects of reversal effect of itraconazole on P-glycoprotein-mediated resistance of anticancer drugs. Biol Pharm Bull. 1999;22:1355–9.

Article  CAS  PubMed  Google Scholar 

Wang W, Dong X, Liu Y, Ni B, Sai N, You L, et al. Itraconazole exerts anti-liver cancer potential through the Wnt, PI3K/AKT/mTOR, and ROS pathways. Biomed Pharmacother. 2020;131:110661.

Article  CAS  PubMed  Google Scholar 

Zhang WBA, Ramzan Z, Williams TA, Subramaniyan I, Edpuganti V, Kallem RR, et al. Itraconazole exerts its antitumor effect in esophageal cancer by suppressing the HER2/AKT signaling pathway. Mol Cancer Ther. 2010;20:1904–.15

Fattahi S, Pilehchian Langroudi M, Akhavan-Niaki H. Hedgehog signaling pathway: epigenetic regulation and role in disease and cancer development. J Cell Physiol. 2018;233:5726–35.

Article  CAS  PubMed  Google Scholar 

Sheng T, Li C, Zhang X, Chi S, He N, Chen K, et al. Activation of the hedgehog pathway in advanced prostate cancer. Mol Cancer. 2004;3:29.

Article  PubMed  PubMed Central 

Comments (0)

No login
gif