Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74:12–49.

Article  PubMed  Google Scholar 

Dai C, Dehm SM, Sharifi N. Targeting the androgen signaling axis in prostate cancer. J Clin Oncol. 2023;41:4267–78.

Article  CAS  PubMed  Google Scholar 

Bishop JL, Thaper D, Vahid S, Davies A, Ketola K, Kuruma H, et al. The master neural transcription factor BRN2 Is an androgen receptor-suppressed driver of neuroendocrine differentiation in prostate cancer. Cancer Discov. 2017;7:54–71.

Article  CAS  PubMed  Google Scholar 

Beltran H, Prandi D, Mosquera JM, Benelli M, Puca L, Cyrta J, et al. Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat Med. 2016;22:298–305.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nyquist MD, Corella A, Coleman I, De Sarkar N, Kaipainen A, Ha G, et al. Combined TP53 and RB1 loss promotes prostate cancer resistance to a spectrum of therapeutics and confers vulnerability to replication stress. Cell Rep. 2020;31:107669.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shukla S, Cyrta J, Murphy DA, Walczak EG, Ran LL, Agrawal P, et al. Aberrant activation of a gastrointestinal transcriptional circuit in prostate cancer mediates castration resistance. Cancer Cell. 2017;32:792–806.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tang FY, Xu D, Wang SQ, Wong CK, Martinez-Fundichely A, Lee CJ, et al. Chromatin profiles classify castration-resistant prostate cancers suggesting therapeutic targets. Science. 2022;376:eabe1505.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Visakorpi T, Hyytinen E, Koivisto P, Tanner M, Keinanen R, Palmberg C, et al. In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat Genet. 1995;9:401–6.

Article  CAS  PubMed  Google Scholar 

Grasso CS, Wu YM, Robinson DR, Cao X, Dhanasekaran SM, Khan AP, et al. The mutational landscape of lethal castration-resistant prostate cancer. Nature. 2012;487:239–43.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015;162:454.

Article  CAS  PubMed  Google Scholar 

Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, et al. Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res. 2008;68:4447–54.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, et al. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res. 2006;66:2815–25.

Article  CAS  PubMed  Google Scholar 

Hofland J, van Weerden WM, Dits NF, Steenbergen J, van Leenders GJ, Jenster G, et al. Evidence of limited contributions for intratumoral steroidogenesis in prostate cancer. Cancer Res. 2010;70:1256–64.

Article  CAS  PubMed  Google Scholar 

Carver BS, Chapinski C, Wongvipat J, Hieronymus H, Chen Y, Chandarlapaty S, et al. Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell. 2011;19:575–86.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Park JW, Lee JK, Sheu KM, Wang L, Balanis NG, Nguyen K, et al. Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage. Science. 2018;362:91–5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Aggarwal R, Huang J, Alumkal JJ, Zhang L, Feng FY, Thomas GV, et al. Clinical and genomic characterization of treatment-emergent small-cell neuroendocrine prostate cancer: a multi-institutional prospective study. J Clin Oncol. 2018;36:2492–503.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li HY, Wang LL, Li Z, Geng X, Li M, Tang Q, et al. SOX2 has dual functions as a regulator in the progression of neuroendocrine prostate cancer. Lab Invest. 2020;100:570–82.

Article  CAS  PubMed  Google Scholar 

Clermont PL, Lin D, Crea F, Wu R, Xue H, Wang Y, et al. Polycomb-mediated silencing in neuroendocrine prostate cancer. Clin Epigenetics. 2015;7:40.

Article  PubMed  PubMed Central  Google Scholar 

Zhang DX, Hu Q, Liu XZ, Ji YB, Chao HP, Liu Y, et al. Intron retention is a hallmark and spliceosome represents a therapeutic vulnerability in aggressive prostate cancer. Nat Commun. 2020;11:2089.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hu R, Lu C, Mostaghel EA, Yegnasubramanian S, Gurel M, Tannahill C, et al. Distinct transcriptional programs mediated by the ligand-dependent full-length androgen receptor and its splice variants in castration-resistant prostate cancer. Cancer Res. 2012;72:3457–62.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yu Z, Chen S, Sowalsky AG, Voznesensky OS, Mostaghel EA, Nelson PS, et al. Rapid induction of androgen receptor splice variants by androgen deprivation in prostate cancer. Clin Cancer Res. 2014;20:1590–600.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li YA, Donmez N, Sahinalp C, Xie N, Wang YW, Xue H, et al. SRRM4 drives neuroendocrine transdifferentiation of prostate adenocarcinoma under androgen receptor pathway inhibition. Eur Urol. 2017;71:68–78.

Article  CAS  PubMed  Google Scholar 

Zhang XT, Coleman IM, Brown LG, True LD, Kollath L, Lucas JM, et al. SRRM4 expression and the loss of REST activity may promote the emergence of the neuroendocrine phenotype in castration-resistant prostate cancer. Clin Cancer Res. 2015;21:4698–708.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee AR, Gan Y, Tang YX, Dong XS. A novel mechanism of SRRM4 in promoting neuroendocrine prostate cancer development via a pluripotency gene network. EBioMedicine. 2018;35:167–77.

Article  PubMed  PubMed Central  Google Scholar 

Jimenez-Vacas JM, Herrero-Aguayo V, Montero-Hidalgo AJ, Gomez-Gomez E, Fuentes-Fayos AC, Leon-Gonzalez AJ, et al. Dysregulation of the splicing machinery is directly associated to aggressiveness of prostate cancer. EBioMedicine. 2020;51:102547.

Article  PubMed  PubMed Central  Google Scholar 

Wang BD, Ceniccola K, Hwang S, Andrawis R, Horvath A, Freedman JA, et al. Alternative splicing promotes tumour aggressiveness and drug resistance in African American prostate cancer. Nat Commun. 2017;8:15921.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Han JH, Xiong J, Wang D, Fu XD. Pre-mRNA splicing: where and when in the nucleus. Trends Cell Biol. 2011;21:336–43.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet. 2008;40:1413–5.

Article  CAS  PubMed  Google Scholar 

Jiang W, Chen L. Alternative splicing: human disease and quantitative analysis from high-throughput sequencing. Comput Struct Biotechnol J. 2021;19:183–95.

Article  CAS  PubMed  Google Scholar 

Marasco LE, Kornblihtt AR. The physiology of alternative splicing. Nat Rev Mol Cell Biol. 2023;24:242–54.

Article  CAS  PubMed  Google Scholar 

Black DL. Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem. 2003;72:291–336.

Article  CAS  PubMed  Google Scholar 

Kahles A, Lehmann KV, Toussaint NC, Huser M, Stark SG, Sachsenberg T, et al. Comprehensive analysis of alternative splicing across tumors from 8,705 patients. Cancer Cell. 2018;34:211–24.e6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rappsilber J, Ryder U, Lamond AI, Mann M. Large-scale proteomic analysis of the human spliceosome. Genome Res. 2002;12:1231–45.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Barbosa-Morais NL, Carmo-Fonseca M, Aparicio S. Systematic genome-wide annotation of spliceosomal proteins reveals differential gene family expansion. Genome Res. 2006;16:66–77.

Article  CAS  PubMed