Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin. 2021;71:209–49.
Rawla P. Epidemiology of prostate cancer. World J Oncol. 2019;10:63–89.
Google Scholar
Elmehrath AO, Afifi AM, Al-Husseini MJ, Saad AM, Wilson N, Shohdy KS, et al. Causes of death among patients with metastatic prostate cancer in the US From 2000 to 2016. JAMA Netw Open. 2021;4:e2119568–e.
Google Scholar
Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer. Eur Urol. 2017;71:630–42.
Google Scholar
Nagireddy S, Qureshi R, Best J, Frech FS, Shah K, Soni Y, et al. Current Treatment Modalities Targeting Tumor Microenvironment in Castration-Resistant Prostate Cancer. In: Birbrair A, editor. Tumor Microenvironment: Novel Concepts. Cham: Springer International Publishing; 2021. p. 295-323.
McCourt C, Maxwell P, Mazzucchelli R, Montironi R, Scarpelli M, Salto-Tellez M, et al. Elevation of c-FLIP in Castrate-Resistant Prostate Cancer Antagonizes Therapeutic Response to Androgen Receptor–Targeted Therapy. Clin Cancer Res. 2012;18:3822.
Google Scholar
Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35:495–516.
Google Scholar
Johnstone RW, Frew AJ, Smyth MJ. The TRAIL apoptotic pathway in cancer onset, progression and therapy. Nat Rev Cancer. 2008;8:782–98.
Google Scholar
Hillert LK, Ivanisenko NV, Espe J, König C, Ivanisenko VA, Kähne T, et al. Long and short isoforms of c-FLIP act as control checkpoints of DED filament assembly. Oncogene. 2020;39:1756–72.
Google Scholar
Ivanisenko NV, Seyrek K, Hillert-Richter LK, König C, Espe J, Bose K, et al. Regulation of extrinsic apoptotic signaling by c-FLIP: towards targeting cancer networks. Trends Cancer. 2022;8:190–209.
Google Scholar
Micheau O, Shirley S, Dufour F. Death receptors as targets in cancer. Br J Pharm. 2013;169:1723–44.
Google Scholar
Snajdauf M, Havlova K, Vachtenheim J, Ozaniak A, Lischke R, Bartunkova J, et al. The TRAIL in the Treatment of Human Cancer: An Update on Clinical Trials. Frontiers in Molecular Biosciences.8.(2021)
Zhang X, Jin T-G, Yang H, DeWolf WC, Khosravi-Far R, Olumi AF. Persistent c-FLIP(L) Expression Is Necessary and Sufficient to Maintain Resistance to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand–Mediated Apoptosis in Prostate Cancer. Cancer Res. 2004;64:7086–91.
Google Scholar
Wilson C, Wilson T, Johnston PG, Longley DB, Waugh DJJ. Interleukin-8 signaling attenuates TRAIL- and chemotherapy-induced apoptosis through transcriptional regulation of c-FLIP in prostate cancer cells. Mol Cancer Therapeutics. 2008;7:2649.
Google Scholar
Nazim UM, Yin H, Park SY. Downregulation of c‑FLIP and upregulation of DR‑5 by cantharidin sensitizes TRAIL‑mediated apoptosis in prostate cancer cells via autophagy flux. Int J Mol Med. 2020;46:280–8.
Google Scholar
White SJ, Ping L, Keller G, Voelkel-Johnson C. Targeting the short form of cFLIP by RNA interference is sufficient to enhance TRAIL sensitivity in PC3 prostate carcinoma cells. Cancer Biol Ther. 2006;5:1618–23.
Google Scholar
Piggott L, Omidvar N, Pérez SM, Eberl M, Clarkson RWE. Suppression of apoptosis inhibitor c-FLIP selectively eliminates breast cancer stem cell activity in response to the anti-cancer agent, TRAIL. Breast Cancer Res. 2011;13:R88.
Google Scholar
Chang JC. Cancer stem cells: Role in tumor growth, recurrence, metastasis, and treatment resistance. Med (Baltim). 2016;95:S20–s5.
Google Scholar
Giancotti GFR, Hayward O, lee KY, Robinson T, Ribeiro da Silva A, et al. The discovery of small-molecule inhibitors of cFLIP that sensitise tumour cells to TNF-related apoptosis-inducing ligand. Academia Oncology.2.(2025)
Hillert LK, Ivanisenko NV, Busse D, Espe J, König C, Peltek SE, et al. Dissecting DISC regulation via pharmacological targeting of caspase-8/c-FLIPL heterodimer. Cell Death Differ. 2020;27:2117–30.
Google Scholar
Yaacoub K, Pedeux R, Lafite P, Jarry U, Aci-Sèche S, Bonnet P, et al. The identification of new c-FLIP inhibitors for restoring apoptosis in TRAIL-Resistant Cancer Cells. Curr Issues Mol Biol. 2024;46:710–28.
Google Scholar
O’Neill AJ, Prencipe M, Dowling C, Fan Y, Mulrane L, Gallagher WM, et al. Characterisation and manipulation of docetaxel resistant prostate cancer cell lines. Mol Cancer. 2011;10:126.
Google Scholar
Parry-Jones A, Spary LK The Wales Cancer Bank (WCB). Open Journal of Bioresources.(2018)
Frame FM, Pellacani D, Collins AT, Maitland NJ Harvesting Human Prostate Tissue Material and Culturing Primary Prostate Epithelial Cells. In: McEwan PIJ, editor. The Nuclear Receptor Superfamily: Methods and Protocols. New York, NY: Springer New York; 2016. p. 181-201.
Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9:671–5.
Google Scholar
Taurozzi AJ, Beekharry R, Wantoch M, Labarthe MC, Walker HF, Seed RI, et al. Spontaneous development of Epstein-Barr Virus associated human lymphomas in a prostate cancer xenograft program. PLoS One. 2017;12:e0188228.
Google Scholar
Bolis M, Bossi D, Vallerga A, Ceserani V, Cavalli M, Impellizzieri D, et al. Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression. Nat Commun. 2021;12:7033.
Google Scholar
Chandrashekar DS, Karthikeyan SK, Korla PK, Patel H, Shovon AR, Athar M, et al. UALCAN: An update to the integrated cancer data analysis platform. Neoplasia. 2022;25:18–27.
Google Scholar
Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi B, et al. UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia. 2017;19:649–58.
Google Scholar
Hu Y, Smyth GK. ELDA: extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays. J Immunol Methods. 2009;347:70–8.
Google Scholar
den Hollander P, Joseph R, Vasaikar S, Kuburich NA, Deshmukh AP, Mani SA Limiting Dilution Tumor Initiation Assay: An In Vivo Approach for the Study of Cancer Stem Cells. In: Kannan N, Beer P, editors. Stem Cell Assays: Methods and Protocols. New York, NY: Springer US; 2022. p. 547-54.
Petrylak DP, Tangen CM, Hussain MHA, Lara PN, Jones JA, Taplin ME, et al. Docetaxel and Estramustine Compared with Mitoxantrone and Prednisone for Advanced Refractory Prostate Cancer. N Engl J Med. 2004;351:1513–20.
Google Scholar
Tannock IF, Wit RD, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer. N Engl J Med. 2004;351:1502–12.
Google Scholar
Grayson KA, Jyotsana N, Ortiz-Otero N, King MR. Overcoming TRAIL-resistance by sensitizing prostate cancer 3D spheroids with taxanes. PLoS One. 2021;16:e0246733.
Google Scholar
Lee WH, Kim SC, Kim SH, Yoon JH, Moon KH, Cheon SH, et al. Docetaxel enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in prostate cancer cells via epigenetic gene regulation by enhancer of zeste homolog 2. World J Mens Health. 2023;41:649–58.
Google Scholar
Grayson KA, Hope JM, Wang W, Reinhart-King CA, King MR. Taxanes sensitize prostate cancer cells to TRAIL-induced apoptotic synergy via endoplasmic reticulum stress. Mol Cancer Ther. 2021;20:833–45.
Google Scholar
Higgins CA, Majkut J, Fox J, Humphreys L, Fiedler GE, Boffey RJ, et al. Abstract B129: Development and preclinical assessment of a first-in-class small-molecule inhibitor of FLIP. Mol Cancer Therapeutics. 2018;17:B129–B.
Google Scholar
Logan IR, McClurg UL, Jones DL, O’Neill DJ, Shaheen FS, Lunec J, et al. Nutlin-3 inhibits androgen receptor-driven c-FLIP expression, resulting in apoptosis of prostate cancer cells. Oncotarget.7.(2016)
Zhang X, Wen X, Peng R, Pan Q, Weng D, Ma Y, et al. A first-in-human phase I study of a novel MDM2/p53 inhibitor alrizomadlin in advanced solid tumors. ESMO Open.9.(2024)
Molife LR, Attard G, Fong PC, Karavasilis V, Reid AHM, Patterson S, et al. Phase II, two-stage, single-arm trial of the histone deacetylase inhibitor (HDACi) romidepsin in metastatic castration-resistant prostate cancer (CRPC). Ann Oncol. 2010;21:109–13.
Google Scholar
Ouyang X, Shi M, Jie F, Bai Y, Shen P, Yu Z, et al. Phase III study of dulanermin (recombinant human tumor necrosis factor-related apoptosis-inducing ligand/Apo2 ligand) combined with vinorelbine and cisplatin in patients with advanced non-small-cell lung cancer. Invest N Drugs. 2018;36:315–22.
Google Scholar
Panner A, James CD, Berger MS, Pieper RO. mTOR controls FLIPS translation and TRAIL sensitivity in glioblastoma multiforme cells. Mol Cell Biol. 2005;25:8809–23.
Google Scholar
Panner A, Nakamura JL, Parsa AT, Rodriguez-Viciana P, Berger MS, Stokoe D, et al. mTOR-independent translational control of the extrinsic cell death pathway by RalA. Mol Cell Biol. 2006;26:7345–57.
Google Scholar
Bleumink M, Köhler R, Giaisi M, Proksch P, Krammer PH, Li-Weber M. Rocaglamide breaks TRAIL resistance in HTLV-1-associated adult T-cell leukemia/lymphoma by translational suppression of c-FLIP expression. Cell Death Differ. 2011;18:362–70.
Google Scholar
Panner A, Crane CA, Weng C, Feletti A, Fang S, Parsa AT, et al. Ubiquitin-specific protease 8 links the PTEN-Akt-AIP4 pathway to the control of FLIPS stability and TRAIL sensitivity in glioblastoma multiforme. Cancer Res. 2010;70:5046–53.
Google Scholar
Panner A, Crane CA, Weng C, Feletti A, Parsa AT, Pieper RO. A novel PTEN-dependent link to ubiquitination controls FLIPS stability and TRAIL sensitivity in glioblastoma multiforme. Cancer Res. 2009;69:7911–6.
Google Scholar
Gao S, Wang H, Lee P, Melamed J, Li CX, Zhang F, et al. Androgen receptor and prostate apoptosis response factor-4 target the c-FLIP gene to determine survival and apoptosis in the prostate gland. J Mol Endocrinol. 2006;36:463–83.
Google Scholar
Raclaw KA, Heemers HV, Kidd EM, Dehm SM, Tindall DJ. Induction of FLIP expression by androgens protects prostate cancer cells from TRAIL-mediated apoptosis. Prostate. 2008;68:1696–706.
Google Scholar
Ge S, Hua X, Chen J, Xiao H, Zhang L, Zhou J, et al. Identification of a costimulatory molecule-related signature for predicting prognostic risk in prostate cancer. Front Genet. 2021;12:666300.
Google Scholar
Misawa A, Takayama K-i, Urano T, Inoue S. Androgen-induced Long Noncoding RNA (lncRNA) SOCS2-AS1 Promotes Cell Growth and Inhibits Apoptosis in Prostate Cancer Cells*. J Biol Chem. 2016;291:17861–80.
Google Scholar
Hirano D, Okada Y, Minei S, Takimoto Y, Nemoto N. Neuroendocrine differentiation in hormone refractory prostate cancer following androgen deprivation therapy. Eur Urol. 2004;45:586–92. discussion 92.
Google Scholar
Beltran H, Demichelis F. Therapy considerations in neuroendocrine prostate cancer: what next? Endocr Relat Cancer. 2021;28:T67–t78.
Google Scholar

