{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:58:51Z","timestamp":1790621931565,"version":"4.1.0"},"reference-count":120,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["2R01CA240290-06A1"],"award-info":[{"award-number":["2R01CA240290-06A1"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA016056"],"award-info":[{"award-number":["P30CA016056"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA240290"],"award-info":[{"award-number":["R01CA240290"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006398","name":"Roswell Park Alliance Foundation, Roswell Park Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006398","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["PC220137; PC220273"],"award-info":[{"award-number":["PC220137; PC220273"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000892","name":"Prostate Cancer Foundation","doi-asserted-by":"publisher","award":["2022CHAL3788"],"award-info":[{"award-number":["2022CHAL3788"]}],"id":[{"id":"10.13039\/100000892","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000892","name":"Prostate Cancer Foundation","doi-asserted-by":"publisher","award":["2022CHAL3788"],"award-info":[{"award-number":["2022CHAL3788"]}],"id":[{"id":"10.13039\/100000892","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The George Decker Endowment"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    BCL-2 has been implicated in prostate cancer (PCa) progression and development of castration-resistant disease (CRPC); however, it remains unclear how the BCL-2- and AR-expressing PCa cell populations evolve across the PCa continuum, how AR molecularly regulates BCL-2 and whether BCL-2 represents a common therapeutic target in heterogeneous CRPC. Here we first show the selective induction of BCL-2 by AR pathway inhibitors (ARPIs). Vectra-based quantitative multiplex immunofluorescence (qmIF) and image mass cytometry (IMC) analyses with single-cell resolution in patient PCa and xenograft models reveal markedly increased BCL-2\n                    <jats:sup>+<\/jats:sup>\n                    (AR\n                    <jats:sup>+<\/jats:sup>\n                    or AR\n                    <jats:sup>-<\/jats:sup>\n                    ) PCa cells in CRPC. Mechanistically, AR represses\n                    <jats:italic>BCL-2<\/jats:italic>\n                    transcription through several AR binding sites and ARPIs relieve this repression. Therapeutic studies in cells, organoids and xenografts support BCL-2 as a shared vulnerability across diverse CRPC subtypes. A Phase Ib clinical trial (NCT03751436) combining enzalutamide and BCL-2 inhibitor venetoclax demonstrated reduced circulating tumor cells in responding patients. In summary, by integrating high-content single-cell level imaging analyses with mechanistic studies, extensive preclinical therapeutic experiments and a Phase Ib clinical trial, our studies herein elucidate the AR\n                    <jats:sup>+\/-<\/jats:sup>\n                    BCL-2\n                    <jats:sup>+\/-<\/jats:sup>\n                    PCa cell subpopulation dynamics and credentials BCL-2 as a vital therapeutic target in heterogeneous CRPC.\n                  <\/jats:p>","DOI":"10.1038\/s41392-026-02700-w","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T14:27:24Z","timestamp":1777645644000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Single-cell imaging analysis, therapeutic modeling and a Phase Ib trial validate BCL-2 as a target across heterogeneous castration-resistant prostate cancer"],"prefix":"10.1038","volume":"11","author":[{"given":"Anmbreen","family":"Jamroze","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2237-1016","authenticated-orcid":false,"given":"Xiaozhuo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surui","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6906-1256","authenticated-orcid":false,"given":"Wen","family":"(Jess) Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Tracz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Jacobi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuhui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent","family":"Nastiuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1195-1998","authenticated-orcid":false,"given":"Jiaoti","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8701-2586","authenticated-orcid":false,"given":"Changmeng","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Puzanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason S.","family":"Kirk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurkamal","family":"Chatta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5029-1174","authenticated-orcid":false,"given":"Dean G.","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"2700_CR1","first-page":"10","volume":"75","author":"RL Siegel","year":"2025","unstructured":"Siegel, R. L., Kratzer, T. B., Giaquinto, A. N., Sung, H. & Jemal, A. Cancer statistics, 2025. CA Cancer J. Clin. 75, 10\u201345 (2025).","journal-title":"CA Cancer J. Clin."},{"key":"2700_CR2","doi-asserted-by":"publisher","first-page":"6916","DOI":"10.1158\/1078-0432.CCR-19-1423","volume":"25","author":"H Beltran","year":"2019","unstructured":"Beltran, H. et al. The role of lineage plasticity in prostate cancer therapy resistance. Clin. Cancer Res. 25, 6916\u20136924 (2019).","journal-title":"Clin. Cancer Res."},{"key":"2700_CR3","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.molcel.2020.10.033","volume":"80","author":"MA Rubin","year":"2020","unstructured":"Rubin, M. A., Bristow, R. G., Thienger, P. D., Dive, C. & Imielinski, M. Impact of lineage plasticity to and from a neuroendocrine phenotype on progression and response in prostate and lung cancers. Mol. Cell 80, 562\u2013577 (2020).","journal-title":"Mol. Cell"},{"key":"2700_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.canlet.2021.06.006","volume":"518","author":"A Jamroze","year":"2021","unstructured":"Jamroze, A., Chatta, G. & Tang, D. G. Androgen receptor (AR) heterogeneity in prostate cancer and therapy resistance. Cancer Lett. 518, 1\u20139 (2021).","journal-title":"Cancer Lett."},{"key":"2700_CR5","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.semcancer.2021.11.001","volume":"82","author":"DG Tang","year":"2022","unstructured":"Tang, D. G. Understanding and targeting prostate cancer cell heterogeneity and plasticity. Semin. Cancer Biol. 82, 68\u201393 (2022).","journal-title":"Semin. Cancer Biol."},{"key":"2700_CR6","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1158\/2159-8290.CD-23-0225","volume":"13","author":"A Davies","year":"2023","unstructured":"Davies, A., Zoubeidi, A., Beltran, H. & Selth, L. A. The transcriptional and epigenetic landscape of cancer cell lineage plasticity. Cancer Discov. 13, 1771\u20131788 (2023).","journal-title":"Cancer Discov."},{"key":"2700_CR7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36253-1","volume":"14","author":"G Chakraborty","year":"2023","unstructured":"Chakraborty, G., Gupta, K. & Kyprianou, N. Epigenetic mechanisms underlying subtype heterogeneity and tumor recurrence in prostate cancer. Nat. Commun. 14, 567 (2023).","journal-title":"Nat. Commun."},{"key":"2700_CR8","first-page":"0005","volume":"1","author":"A Jamroze","year":"2024","unstructured":"Jamroze, A., Liu, X. & Tang, D. G. Treatment-induced stemness and lineage plasticity in driving prostate cancer therapy resistance. Cancer Heterog. Plast. 1, 0005 (2024).","journal-title":"Cancer Heterog. Plast."},{"key":"2700_CR9","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1002\/path.1711600409","volume":"160","author":"JA de Winter","year":"1990","unstructured":"de Winter, J. A. et al. Androgen receptor heterogeneity in human prostatic carcinomas visualized by immunohistochemistry. J. Pathol. 160, 329\u2013332 (1990).","journal-title":"J. Pathol."},{"key":"2700_CR10","first-page":"735","volume":"144","author":"JA Ruizeveld de Winter","year":"1994","unstructured":"Ruizeveld de Winter, J. A. et al. Androgen receptor status in localized and locally progressive hormone refractory human prostate cancer. Am. J. Pathol. 144, 735\u2013746 (1994).","journal-title":"Am. J. Pathol."},{"key":"2700_CR11","first-page":"3068","volume":"55","author":"A Hobisch","year":"1995","unstructured":"Hobisch, A. et al. Distant metastases from prostatic carcinoma express androgen receptor protein. Cancer Res. 55, 3068\u20133072 (1995).","journal-title":"Cancer Res."},{"key":"2700_CR12","doi-asserted-by":"publisher","first-page":"9209","DOI":"10.1158\/0008-5472.CAN-04-2442","volume":"64","author":"RB Shah","year":"2004","unstructured":"Shah, R. B. et al. Androgen-independent prostate cancer is a heterogeneous group of diseases: lessons from a rapid autopsy program. Cancer Res. 64, 9209\u20139216 (2004).","journal-title":"Cancer Res."},{"key":"2700_CR13","doi-asserted-by":"publisher","first-page":"11897","DOI":"10.1158\/0008-5472.CAN-06-2497","volume":"66","author":"JN Davis","year":"2006","unstructured":"Davis, J. N. et al. Elevated E2F1 inhibits transcription of the androgen receptor in metastatic hormone-resistant prostate cancer. Cancer Res. 66, 11897\u201311906 (2006).","journal-title":"Cancer Res."},{"key":"2700_CR14","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.stem.2012.03.009","volume":"10","author":"J Qin","year":"2012","unstructured":"Qin, J. et al. The PSA(-\/lo) prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration. Cell Stem Cell 10, 556\u2013569 (2012).","journal-title":"Cell Stem Cell"},{"key":"2700_CR15","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.ccr.2012.07.016","volume":"22","author":"J Domingo-Domenech","year":"2012","unstructured":"Domingo-Domenech, J. et al. Suppression of acquired docetaxel resistance in prostate cancer through depletion of notch- and hedgehog-dependent tumor-initiating cells. Cancer Cell 22, 373\u2013388 (2012).","journal-title":"Cancer Cell"},{"key":"2700_CR16","doi-asserted-by":"publisher","first-page":"e74438","DOI":"10.1371\/journal.pone.0074438","volume":"8","author":"RR Finones","year":"2013","unstructured":"Finones, R. R. et al. Early human prostate adenocarcinomas harbor androgen-independent cancer cells. PLoS ONE 8, e74438 (2013).","journal-title":"PLoS ONE"},{"key":"2700_CR17","doi-asserted-by":"publisher","first-page":"23959","DOI":"10.18632\/oncotarget.4260","volume":"6","author":"X Liu","year":"2015","unstructured":"Liu, X. et al. Systematic dissection of phenotypic, functional, and tumorigenic heterogeneity of human prostate cancer cells. Oncotarget 6, 23959\u201323986 (2015).","journal-title":"Oncotarget"},{"key":"2700_CR18","doi-asserted-by":"publisher","first-page":"4505","DOI":"10.1158\/1078-0432.CCR-15-2956","volume":"22","author":"X Chen","year":"2016","unstructured":"Chen, X. et al. Defining a population of stem-like human prostate cancer cells that can generate and propagate castration-resistant prostate cancer. Clin. Cancer Res. 22, 4505\u20134516 (2016).","journal-title":"Clin. Cancer Res."},{"key":"2700_CR19","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/j.ccell.2017.09.003","volume":"32","author":"EG Bluemn","year":"2017","unstructured":"Bluemn, E. G. et al. Androgen receptor pathway-independent prostate cancer is sustained through FGF signaling. Cancer Cell 32, 474\u2013489.e476 (2017).","journal-title":"Cancer Cell"},{"key":"2700_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06067-7","volume":"9","author":"Q Li","year":"2018","unstructured":"Li, Q. et al. Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses. Nat. Commun. 9, 3600 (2018).","journal-title":"Nat. Commun."},{"key":"2700_CR21","doi-asserted-by":"publisher","first-page":"4492","DOI":"10.1172\/JCI128212","volume":"129","author":"MP Labrecque","year":"2019","unstructured":"Labrecque, M. P. et al. Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer. J. Clin. Invest. 129, 4492\u20134505 (2019).","journal-title":"J. Clin. Invest."},{"key":"2700_CR22","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1038\/s43018-023-00539-6","volume":"4","author":"M Bakht","year":"2023","unstructured":"Bakht, M. et al. Landscape of prostate-specific membrane antigen heterogeneity and regulation in AR-positive and AR-negative metastatic prostate cancer. Nat. Cancer 4, 699\u2013715 (2023).","journal-title":"Nat. Cancer"},{"key":"2700_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32701-6","volume":"13","author":"TC Westbrook","year":"2022","unstructured":"Westbrook, T. C. et al. Transcriptional profiling of matched patient biopsies clarifies molecular determinants of enzalutamide-induced lineage plasticity. Nat. Commun. 13, 5345 (2022).","journal-title":"Nat. Commun."},{"key":"2700_CR24","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/nm.2284","volume":"17","author":"C Liu","year":"2011","unstructured":"Liu, C. et al. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat. Med. 17, 211\u2013215 (2011).","journal-title":"Nat. Med."},{"key":"2700_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14270","volume":"8","author":"C Liu","year":"2017","unstructured":"Liu, C. et al. MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes. Nat. Commun. 8, 14270 (2017).","journal-title":"Nat. Commun."},{"key":"2700_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/celldisc.2016.41","volume":"2","author":"CR Jeter","year":"2016","unstructured":"Jeter, C. R. et al. NANOG reprograms prostate cancer cells to castration resistance via dynamically repressing and engaging the AR\/FOXA1 signaling axis. Cell Discov. 2, 16041 (2016).","journal-title":"Cell Discov."},{"key":"2700_CR27","first-page":"6940","volume":"52","author":"TJ McDonnell","year":"1992","unstructured":"McDonnell, T. J. et al. Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer. Cancer Res. 52, 6940\u20136944 (1992).","journal-title":"Cancer Res."},{"key":"2700_CR28","first-page":"4438","volume":"55","author":"AJ Raffo","year":"1995","unstructured":"Raffo, A. J. et al. Overexpression of bcl-2 protects prostate cancer cells from apoptosis in vitro and confers resistance to androgen depletion in vivo. Cancer Res. 55, 4438\u20134445 (1995).","journal-title":"Cancer Res."},{"key":"2700_CR29","doi-asserted-by":"publisher","first-page":"5241","DOI":"10.1073\/pnas.93.11.5241","volume":"93","author":"DG Tang","year":"1996","unstructured":"Tang, D. G., Chen, Y. Q. & Honn, K. V. Arachidonate lipoxygenases as essential regulators of cell survival and apoptosis. Proc. Natl. Acad. Sci. USA 93, 5241\u20135246 (1996).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2700_CR30","first-page":"1557","volume":"148","author":"L Bubendorf","year":"1996","unstructured":"Bubendorf, L. et al. Prognostic significance of Bcl-2 in clinically localized prostate cancer. Am. J. Pathol. 148, 1557\u20131565 (1996).","journal-title":"Am. J. Pathol."},{"key":"2700_CR31","doi-asserted-by":"publisher","first-page":"1880","DOI":"10.1016\/S0022-5347(01)64157-0","volume":"158","author":"MA Noordzij","year":"1997","unstructured":"Noordzij, M. A., Bogdanowicz, J. F., van Krimpen, C., van der Kwast, T. H. & van Steenbrugge, G. J. The prognostic value of pretreatment expression of androgen receptor and bcl-2 in hormonally treated prostate cancer patients. J. Urol. 158, 1880\u20131884 (1997).","journal-title":"J. Urol."},{"key":"2700_CR32","first-page":"3466","volume":"58","author":"DG Tang","year":"1998","unstructured":"Tang, D. G., Li, L., Chopra, D. P. & Porter, A. T. Extended survivability of prostate cancer cells in the absence of trophic factors: increased proliferation, evasion of apoptosis, and the role of apoptosis proteins. Cancer Res. 58, 3466\u20133479 (1998).","journal-title":"Cancer Res."},{"key":"2700_CR33","doi-asserted-by":"publisher","first-page":"7342","DOI":"10.1038\/sj.onc.1204926","volume":"20","author":"SD Catz","year":"2001","unstructured":"Catz, S. D. & Johnson, J. L. Transcriptional regulation of bcl-2 by nuclear factor kappa B and its significance in prostate cancer. Oncogene 20, 7342\u20137351 (2001).","journal-title":"Oncogene"},{"key":"2700_CR34","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/S1535-6108(02)00034-X","volume":"1","author":"F Vanden Abeele","year":"2002","unstructured":"Vanden Abeele, F. et al. Bcl-2-dependent modulation of Ca(2+) homeostasis and store-operated channels in prostate cancer cells. Cancer Cell 1, 169\u2013179 (2002).","journal-title":"Cancer Cell"},{"key":"2700_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0360-3016(02)04468-1","volume":"56","author":"CJ Rosser","year":"2003","unstructured":"Rosser, C. J. et al. Bcl-2 is significantly overexpressed in localized radio-recurrent prostate carcinoma, compared with localized radio-naive prostate carcinoma. Int J. Radiat. Oncol. Biol. Phys. 56, 1\u20136 (2003).","journal-title":"Int J. Radiat. Oncol. Biol. Phys."},{"key":"2700_CR36","doi-asserted-by":"publisher","first-page":"2161","DOI":"10.1038\/sj.onc.1207326","volume":"23","author":"H Huang","year":"2004","unstructured":"Huang, H., Zegarra-Moro, O. L., Benson, D. & Tindall, D. J. Androgens repress Bcl-2 expression via activation of the retinoblastoma (RB) protein in prostate cancer cells. Oncogene 23, 2161\u20132176 (2004).","journal-title":"Oncogene"},{"key":"2700_CR37","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1038\/sj.onc.1208385","volume":"24","author":"JW Liu","year":"2005","unstructured":"Liu, J. W. et al. Induction of prosurvival molecules by apoptotic stimuli: involvement of FOXO3a and ROS. Oncogene 24, 2020\u20132031 (2005).","journal-title":"Oncogene"},{"key":"2700_CR38","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1073\/pnas.0510652103","volume":"103","author":"S Wang","year":"2006","unstructured":"Wang, S. et al. Pten deletion leads to the expansion of a prostatic stem\/progenitor cell subpopulation and tumor initiation. Proc. Natl. Acad. Sci. USA 103, 1480\u20131485 (2006).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2700_CR39","doi-asserted-by":"publisher","first-page":"6116","DOI":"10.1158\/1078-0432.CCR-06-0147","volume":"12","author":"T Yoshino","year":"2006","unstructured":"Yoshino, T. et al. Bcl-2 expression as a predictive marker of hormone-refractory prostate cancer treated with taxane-based chemotherapy. Clin. Cancer Res. 12, 6116\u20136124 (2006).","journal-title":"Clin. Cancer Res."},{"key":"2700_CR40","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1038\/cr.2007.12","volume":"17","author":"Y Lin","year":"2007","unstructured":"Lin, Y., Fukuchi, J., Hiipakka, R. A., Kokontis, J. M. & Xiang, J. Up-regulation of Bcl-2 is required for the progression of prostate cancer cells from an androgen-dependent to an androgen-independent growth stage. Cell Res. 17, 531\u2013536 (2007).","journal-title":"Cell Res."},{"key":"2700_CR41","doi-asserted-by":"publisher","first-page":"2220","DOI":"10.1002\/stem.135","volume":"27","author":"PE Burger","year":"2009","unstructured":"Burger, P. E. et al. High aldehyde dehydrogenase activity: a novel functional marker of murine prostate stem\/progenitor cells. Stem Cells 27, 2220\u20132228 (2009).","journal-title":"Stem Cells"},{"key":"2700_CR42","doi-asserted-by":"publisher","first-page":"2193","DOI":"10.1158\/0008-5472.CAN-10-1791","volume":"71","author":"D Zhang","year":"2011","unstructured":"Zhang, D. et al. PrLZ protects prostate cancer cells from apoptosis induced by androgen deprivation via the activation of Stat3\/Bcl-2 pathway. Cancer Res. 71, 2193\u20132202 (2011).","journal-title":"Cancer Res."},{"key":"2700_CR43","doi-asserted-by":"publisher","first-page":"14220","DOI":"10.18632\/oncotarget.7303","volume":"7","author":"K Rycaj","year":"2016","unstructured":"Rycaj, K. et al. Longitudinal tracking of subpopulation dynamics and molecular changes during LNCaP cell castration and identification of inhibitors that could target the PSA-\/lo castration-resistant cells. Oncotarget 7, 14220\u201314240 (2016).","journal-title":"Oncotarget"},{"key":"2700_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10798","volume":"7","author":"D Zhang","year":"2016","unstructured":"Zhang, D. et al. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer. Nat. Commun. 7, 10798 (2016).","journal-title":"Nat. Commun."},{"key":"2700_CR45","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.eururo.2016.04.019","volume":"71","author":"K Saeed","year":"2017","unstructured":"Saeed, K. et al. Comprehensive drug testing of patient-derived conditionally reprogrammed cells from castration-resistant prostate cancer. Eur. Urol. 71, 319\u2013327 (2017).","journal-title":"Eur. Urol."},{"key":"2700_CR46","doi-asserted-by":"publisher","first-page":"7656","DOI":"10.7150\/thno.44567","volume":"10","author":"Y Li","year":"2020","unstructured":"Li, Y. et al. TGF-beta causes Docetaxel resistance in Prostate Cancer via the induction of Bcl-2 by acetylated KLF5 and Protein Stabilization. Theranostics 10, 7656\u20137670 (2020).","journal-title":"Theranostics"},{"key":"2700_CR47","doi-asserted-by":"publisher","first-page":"2340","DOI":"10.1158\/1078-0432.CCR-20-3260","volume":"27","author":"Y Liang","year":"2021","unstructured":"Liang, Y. et al. Emergence of enzalutamide resistance in prostate cancer is associated with BCL-2 and IKKB dependencies. Clin. Cancer Res. 27, 2340\u20132351 (2021).","journal-title":"Clin. Cancer Res."},{"key":"2700_CR48","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1158\/1078-0432.CCR-19-0775","volume":"26","author":"AN Corella","year":"2020","unstructured":"Corella, A. N. et al. Identification of therapeutic vulnerabilities in small-cell neuroendocrine prostate cancer. Clin. Cancer Res. 26, 1667\u20131677 (2020).","journal-title":"Clin. Cancer Res."},{"key":"2700_CR49","doi-asserted-by":"publisher","first-page":"e179998","DOI":"10.1172\/JCI179998","volume":"134","author":"D Westaby","year":"2024","unstructured":"Westaby, D. et al. BCL2 expression is enriched in advanced prostate cancer with features of lineage plasticity. J. Clin. Invest. 134, e179998 (2024).","journal-title":"J. Clin. Invest."},{"key":"2700_CR50","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115779","volume":"44","author":"R Hirani","year":"2025","unstructured":"Hirani, R. et al. BCL2 drives castration resistance in castration-sensitive prostate cancer by orchestrating reciprocal crosstalk between oncogenic pathways. Cell Rep. 44, 115779 (2025).","journal-title":"Cell Rep."},{"key":"2700_CR51","first-page":"2891","volume":"5","author":"M Gleave","year":"1999","unstructured":"Gleave, M. et al. Progression to androgen independence is delayed by adjuvant treatment with antisense Bcl-2 oligodeoxynucleotides after castration in the LNCaP prostate tumor model. Clin. Cancer Res. 5, 2891\u20132898 (1999).","journal-title":"Clin. Cancer Res."},{"key":"2700_CR52","first-page":"3920","volume":"7","author":"KN Chi","year":"2001","unstructured":"Chi, K. N. et al. A phase I dose-finding study of combined treatment with an antisense Bcl-2 oligonucleotide (Genasense) and mitoxantrone in patients with metastatic hormone-refractory prostate cancer. Clin. Cancer Res. 7, 3920\u20133927 (2001).","journal-title":"Clin. Cancer Res."},{"key":"2700_CR53","doi-asserted-by":"publisher","first-page":"5048","DOI":"10.1158\/1078-0432.CCR-03-0701","volume":"10","author":"AW Tolcher","year":"2004","unstructured":"Tolcher, A. W. et al. A Phase I pharmacokinetic and biological correlative study of oblimersen sodium (genasense, g3139), an antisense oligonucleotide to the bcl-2 mRNA, and of docetaxel in patients with hormone-refractory prostate cancer. Clin. Cancer Res. 10, 5048\u20135057 (2004).","journal-title":"Clin. Cancer Res."},{"key":"2700_CR54","doi-asserted-by":"publisher","first-page":"3854","DOI":"10.1158\/1078-0432.CCR-04-2145","volume":"11","author":"AW Tolcher","year":"2005","unstructured":"Tolcher, A. W. et al. A phase II, pharmacokinetic, and biological correlative study of oblimersen sodium and docetaxel in patients with hormone-refractory prostate cancer. Clin. Cancer Res. 11, 3854\u20133861 (2005).","journal-title":"Clin. Cancer Res."},{"key":"2700_CR55","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1093\/annonc\/mdn784","volume":"20","author":"CN Sternberg","year":"2009","unstructured":"Sternberg, C. N. et al. Docetaxel plus oblimersen sodium (Bcl-2 antisense oligonucleotide): an EORTC multicenter, randomized phase II study in patients with castration-resistant prostate cancer. Ann. Oncol. 20, 1264\u20131269 (2009).","journal-title":"Ann. Oncol."},{"key":"2700_CR56","doi-asserted-by":"publisher","first-page":"8843","DOI":"10.1158\/0008-5472.CAN-08-0127","volume":"68","author":"S Sonoke","year":"2008","unstructured":"Sonoke, S. et al. Tumor regression in mice by delivery of Bcl-2 small interfering RNA with pegylated cationic liposomes. Cancer Res. 68, 8843\u20138851 (2008).","journal-title":"Cancer Res."},{"key":"2700_CR57","doi-asserted-by":"publisher","first-page":"3172","DOI":"10.1158\/1078-0432.CCR-08-2985","volume":"15","author":"G Liu","year":"2009","unstructured":"Liu, G. et al. An open-label, multicenter, phase I\/II study of single-agent AT-101 in men with castrate-resistant prostate cancer. Clin. Cancer Res. 15, 3172\u20133176 (2009).","journal-title":"Clin. Cancer Res."},{"key":"2700_CR58","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1007\/s10637-019-00807-2","volume":"38","author":"MN Stein","year":"2020","unstructured":"Stein, M. N. et al. A phase I study of AT-101, a BH3 mimetic, in combination with paclitaxel and carboplatin in solid tumors. Invest N. Drugs 38, 855\u2013865 (2020).","journal-title":"Invest N. Drugs"},{"key":"2700_CR59","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1038\/sj.onc.1209830","volume":"26","author":"J An","year":"2007","unstructured":"An, J., Chervin, A. S., Nie, A., Ducoff, H. S. & Huang, Z. Overcoming the radioresistance of prostate cancer cells with a novel Bcl-2 inhibitor. Oncogene 26, 652\u2013661 (2007).","journal-title":"Oncogene"},{"key":"2700_CR60","doi-asserted-by":"publisher","first-page":"4377","DOI":"10.1158\/0008-5472.CAN-07-6590","volume":"68","author":"L Wang","year":"2008","unstructured":"Wang, L. et al. WL-276, an antagonist against Bcl-2 proteins, overcomes drug resistance and suppresses prostate tumor growth. Cancer Res. 68, 4377\u20134383 (2008).","journal-title":"Cancer Res."},{"key":"2700_CR61","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/nm.3048","volume":"19","author":"AJ Souers","year":"2013","unstructured":"Souers, A. J. et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat. Med. 19, 202\u2013208 (2013).","journal-title":"Nat. Med."},{"key":"2700_CR62","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.ccr.2013.06.002","volume":"24","author":"F Vaillant","year":"2013","unstructured":"Vaillant, F. et al. Targeting BCL-2 with the BH3 mimetic ABT-199 in estrogen receptor-positive breast cancer. Cancer Cell 24, 120\u2013129 (2013).","journal-title":"Cancer Cell"},{"key":"2700_CR63","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1056\/NEJMoa1513257","volume":"374","author":"AW Roberts","year":"2016","unstructured":"Roberts, A. W. et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N. Engl. J. Med. 374, 311\u2013322 (2016).","journal-title":"N. Engl. J. Med."},{"key":"2700_CR64","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1158\/2159-8290.CD-16-0313","volume":"6","author":"M Konopleva","year":"2016","unstructured":"Konopleva, M. et al. Efficacy and biological correlates of response in a Phase II study of venetoclax monotherapy in patients with acute myelogenous leukemia. Cancer Discov. 6, 1106\u20131117 (2016).","journal-title":"Cancer Discov."},{"key":"2700_CR65","doi-asserted-by":"publisher","first-page":"5455","DOI":"10.1158\/1078-0432.CCR-21-4037","volume":"28","author":"J Deng","year":"2022","unstructured":"Deng, J. et al. Lisaftoclax (APG-2575) is a novel BCL-2 inhibitor with robust antitumor activity in preclinical models of hematologic malignancy. Clin. Cancer Res. 28, 5455\u20135468 (2022).","journal-title":"Clin. Cancer Res."},{"key":"2700_CR66","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1158\/1078-0432.CCR-22-0978","volume":"29","author":"Y Zhai","year":"2023","unstructured":"Zhai, Y. et al. Lisaftoclax in combination with alrizomadlin overcomes venetoclax resistance in acute myeloid leukemia and acute lymphoblastic leukemia: preclinical studies. Clin. Cancer Res. 29, 183\u2013196 (2023).","journal-title":"Clin. Cancer Res."},{"key":"2700_CR67","doi-asserted-by":"publisher","first-page":"2385","DOI":"10.1158\/1078-0432.CCR-22-3321","volume":"29","author":"S Ailawadhi","year":"2023","unstructured":"Ailawadhi, S. et al. Novel BCL-2 inhibitor lisaftoclax in relapsed or refractory chronic lymphocytic leukemia and other hematologic malignancies: first-in-human open-label trial. Clin. Cancer Res. 29, 2385\u20132393 (2023).","journal-title":"Clin. Cancer Res."},{"key":"2700_CR68","doi-asserted-by":"publisher","first-page":"7836","DOI":"10.1021\/acs.jmedchem.4c00027","volume":"67","author":"Y Guo","year":"2024","unstructured":"Guo, Y. et al. Discovery of the clinical candidate sonrotoclax (BGB-11417), a highly potent and selective inhibitor for both WT and G101V mutant Bcl-2. J. Med. Chem. 67, 7836\u20137858 (2024).","journal-title":"J. Med. Chem."},{"key":"2700_CR69","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1182\/blood.2023019706","volume":"143","author":"J Liu","year":"2024","unstructured":"Liu, J. et al. Sonrotoclax overcomes BCL2 G101V mutation-induced venetoclax resistance in preclinical models of hematologic malignancy. Blood 143, 1825\u20131836 (2024).","journal-title":"Blood"},{"key":"2700_CR70","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s00280-025-04840-2","volume":"95","author":"S Perimbeti","year":"2025","unstructured":"Perimbeti, S. et al. Phase Ib study of enzalutamide with venetoclax in patients with metastatic castration-resistant prostate cancer. Cancer Chemother. Pharmacol. 95, 115 (2025).","journal-title":"Cancer Chemother. Pharmacol."},{"key":"2700_CR71","doi-asserted-by":"publisher","first-page":"2596","DOI":"10.1016\/j.celrep.2016.11.010","volume":"17","author":"X Liu","year":"2016","unstructured":"Liu, X. et al. Low CD38 identifies progenitor-like inflammation-associated luminal cells that can initiate human prostate cancer and predict poor outcome. Cell Rep. 17, 2596\u20132606 (2016).","journal-title":"Cell Rep."},{"key":"2700_CR72","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.eururo.2013.08.011","volume":"66","author":"P Rajan","year":"2014","unstructured":"Rajan, P. et al. Next-generation sequencing of advanced prostate cancer treated with androgen-deprivation therapy. Eur. Urol. 66, 32\u201339 (2014).","journal-title":"Eur. Urol."},{"key":"2700_CR73","doi-asserted-by":"publisher","first-page":"379","DOI":"10.3390\/cancers10100379","volume":"10","author":"NV Sharma","year":"2018","unstructured":"Sharma, N. V. et al. Identification of the transcription factor relationships associated with androgen deprivation therapy response and metastatic progression in prostate cancer. Cancers 10, 379 (2018).","journal-title":"Cancers"},{"key":"2700_CR74","doi-asserted-by":"publisher","unstructured":"Liu, X. et al. Increasing stemness drives prostate cancer progression, plasticity, therapy resistance and poor patient survival. Preprint at https:\/\/doi.org\/10.1101\/2025.04.27.650697 (2025).","DOI":"10.1101\/2025.04.27.650697"},{"key":"2700_CR75","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/j.eururo.2021.12.039","volume":"81","author":"Q Cheng","year":"2022","unstructured":"Cheng, Q. et al. Pre-existing castration-resistant prostate cancer-like cells in primary prostate cancer promote resistance to hormonal therapy. Eur. Urol. 81, 446\u2013455 (2022).","journal-title":"Eur. Urol."},{"key":"2700_CR76","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1016\/j.stem.2024.05.008","volume":"31","author":"JS Kirk","year":"2024","unstructured":"Kirk, J. S. et al. Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells. Cell Stem Cell 31, 1203\u20131221.e1207 (2024).","journal-title":"Cell Stem Cell"},{"key":"2700_CR77","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-02973-1","volume":"11","author":"X Long","year":"2020","unstructured":"Long, X. et al. Immune signature driven by ADT-induced immune microenvironment remodeling in prostate cancer is correlated with recurrence-free survival and immune infiltration. Cell Death Dis. 11, 779 (2020).","journal-title":"Cell Death Dis."},{"key":"2700_CR78","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe1505","volume":"376","author":"F Tang","year":"2022","unstructured":"Tang, F. et al. Chromatin profiles classify castration-resistant prostate cancers suggesting therapeutic targets. Science 376, eabe1505 (2022).","journal-title":"Science"},{"key":"2700_CR79","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1128\/MCB.05958-11","volume":"32","author":"PY Tan","year":"2012","unstructured":"Tan, P. Y. et al. Integration of regulatory networks by NKX3-1 promotes androgen-dependent prostate cancer survival. Mol. Cell Biol. 32, 399\u2013414 (2012).","journal-title":"Mol. Cell Biol."},{"key":"2700_CR80","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1038\/s41588-022-01168-y","volume":"54","author":"SC Baca","year":"2022","unstructured":"Baca, S. C. et al. Genetic determinants of chromatin reveal prostate cancer risk mediated by context-dependent gene regulation. Nat. Genet 54, 1364\u20131375 (2022).","journal-title":"Nat. Genet"},{"key":"2700_CR81","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.ccr.2010.03.018","volume":"17","author":"J Yu","year":"2010","unstructured":"Yu, J. et al. An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression. Cancer Cell 17, 443\u2013454 (2010).","journal-title":"Cancer Cell"},{"key":"2700_CR82","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.ccr.2011.09.001","volume":"20","author":"C Cai","year":"2011","unstructured":"Cai, C. et al. Androgen receptor gene expression in prostate cancer is directly suppressed by the androgen receptor through recruitment of lysine-specific demethylase 1. Cancer Cell 20, 457\u2013471 (2011).","journal-title":"Cancer Cell"},{"key":"2700_CR83","doi-asserted-by":"publisher","first-page":"3962","DOI":"10.1038\/emboj.2011.328","volume":"30","author":"B Sahu","year":"2011","unstructured":"Sahu, B. et al. Dual role of FoxA1 in androgen receptor binding to chromatin, androgen signalling and prostate cancer. EMBO J. 30, 3962\u20133976 (2011).","journal-title":"EMBO J."},{"key":"2700_CR84","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1158\/0008-5472.CAN-12-2350","volume":"73","author":"B Sahu","year":"2013","unstructured":"Sahu, B. et al. FoxA1 specifies unique androgen and glucocorticoid receptor binding events in prostate cancer cells. Cancer Res. 73, 1570\u20131580 (2013).","journal-title":"Cancer Res."},{"key":"2700_CR85","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1038\/nature13229","volume":"510","author":"IA Asangani","year":"2014","unstructured":"Asangani, I. A. et al. Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer. Nature 510, 278\u2013282 (2014).","journal-title":"Nature"},{"key":"2700_CR86","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1158\/1078-0432.CCR-13-1863","volume":"20","author":"Z Yu","year":"2014","unstructured":"Yu, Z. et al. Rapid induction of androgen receptor splice variants by androgen deprivation in prostate cancer. Clin. Cancer Res. 20, 1590\u20131600 (2014).","journal-title":"Clin. Cancer Res."},{"key":"2700_CR87","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1016\/j.ajpath.2014.04.010","volume":"184","author":"M Knuuttila","year":"2014","unstructured":"Knuuttila, M. et al. Castration induces up-regulation of intratumoral androgen biosynthesis and androgen receptor expression in an orthotopic VCaP human prostate cancer xenograft model. Am. J. Pathol. 184, 2163\u20132173 (2014).","journal-title":"Am. J. Pathol."},{"key":"2700_CR88","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.ajpath.2017.08.036","volume":"188","author":"M Knuuttila","year":"2018","unstructured":"Knuuttila, M. et al. Antiandrogens reduce intratumoral androgen concentrations and induce androgen receptor expression in castration-resistant prostate cancer xenografts. Am. J. Pathol. 188, 216\u2013228 (2018).","journal-title":"Am. J. Pathol."},{"key":"2700_CR89","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.ccell.2019.01.008","volume":"35","author":"L Cato","year":"2019","unstructured":"Cato, L. et al. ARv7 represses tumor-suppressor genes in castration-resistant prostate cancer. Cancer Cell 35, 401\u2013413.e406 (2019).","journal-title":"Cancer Cell"},{"key":"2700_CR90","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.canlet.2021.07.013","volume":"519","author":"J Liang","year":"2021","unstructured":"Liang, J. et al. Androgen receptor splice variant 7 functions independently of the full length receptor in prostate cancer cells. Cancer Lett. 519, 172\u2013184 (2021).","journal-title":"Cancer Lett."},{"key":"2700_CR91","doi-asserted-by":"publisher","first-page":"e73396","DOI":"10.7554\/eLife.73396","volume":"11","author":"S Kim","year":"2022","unstructured":"Kim, S. et al. AR-V7 exhibits non-canonical mechanisms of nuclear import and chromatin engagement in castrate-resistant prostate cancer. Elife 11, e73396 (2022).","journal-title":"Elife"},{"key":"2700_CR92","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104287","volume":"25","author":"R Huhtaniemi","year":"2022","unstructured":"Huhtaniemi, R. et al. High intratumoral dihydrotestosterone is associated with antiandrogen resistance in VCaP prostate cancer xenografts in castrated mice. iScience 25, 104287 (2022).","journal-title":"iScience"},{"key":"2700_CR93","doi-asserted-by":"publisher","first-page":"e168649","DOI":"10.1172\/JCI168649","volume":"134","author":"D Han","year":"2024","unstructured":"Han, D. et al. Androgen receptor splice variants drive castration-resistant prostate cancer metastasis by activating distinct transcriptional programs. J. Clin. Invest. 134, e168649 (2024).","journal-title":"J. Clin. Invest."},{"key":"2700_CR94","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1093\/nar\/gkad1126","volume":"52","author":"L Helminen","year":"2024","unstructured":"Helminen, L. et al. Chromatin accessibility and pioneer factor FOXA1 restrict glucocorticoid receptor action in prostate cancer. Nucleic Acids Res. 52, 625\u2013642 (2024).","journal-title":"Nucleic Acids Res."},{"key":"2700_CR95","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1101\/gr.280224.124","volume":"35","author":"J Hiltunen","year":"2025","unstructured":"Hiltunen, J. et al. Androgen receptor-mediated assisted loading of the glucocorticoid receptor modulates transcriptional responses in prostate cancer cells. Genome Res. 35, 1717\u20131732 (2025).","journal-title":"Genome Res."},{"key":"2700_CR96","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.115089","volume":"44","author":"L Poluben","year":"2025","unstructured":"Poluben, L. et al. Increased nuclear factor I-mediated chromatin access drives transition to androgen receptor splice variant dependence in prostate cancer. Cell Rep. 44, 115089 (2025).","journal-title":"Cell Rep."},{"key":"2700_CR97","doi-asserted-by":"publisher","first-page":"3663","DOI":"10.1158\/0008-5472.CAN-15-0381","volume":"75","author":"D Xu","year":"2015","unstructured":"Xu, D. et al. Androgen receptor splice variants dimerize to transactivate target genes. Cancer Res. 75, 3663\u20133671 (2015).","journal-title":"Cancer Res."},{"key":"2700_CR98","doi-asserted-by":"publisher","first-page":"5880","DOI":"10.1093\/nar\/gkv262","volume":"43","author":"SC Chan","year":"2015","unstructured":"Chan, S. C. et al. Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies. Nucleic Acids Res. 43, 5880\u20135897 (2015).","journal-title":"Nucleic Acids Res."},{"key":"2700_CR99","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.18632\/oncotarget.1802","volume":"5","author":"B Cao","year":"2014","unstructured":"Cao, B. et al. Androgen receptor splice variants activating the full-length receptor in mediating resistance to androgen-directed therapy. Oncotarget 5, 1646\u20131656 (2014).","journal-title":"Oncotarget"},{"key":"2700_CR100","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2021.128448","volume":"55","author":"A Bhumireddy","year":"2022","unstructured":"Bhumireddy, A. et al. Design, synthesis, and biological evaluation of phenyl thiazole-based AR-V7 degraders. Bioorg. Med. Chem. Lett. 55, 128448 (2022).","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2700_CR101","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1016\/j.cell.2013.11.012","volume":"155","author":"VK Arora","year":"2013","unstructured":"Arora, V. K. et al. Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell 155, 1309\u20131322 (2013).","journal-title":"Cell"},{"key":"2700_CR102","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4972","volume":"5","author":"HJ Jin","year":"2014","unstructured":"Jin, H. J., Zhao, J. C., Wu, L., Kim, J. & Yu, J. Cooperativity and equilibrium with FOXA1 define the androgen receptor transcriptional program. Nat. Commun. 5, 3972 (2014).","journal-title":"Nat. Commun."},{"key":"2700_CR103","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/j.trecan.2018.09.003","volume":"4","author":"D Zhang","year":"2018","unstructured":"Zhang, D., Zhao, S., Li, X., Kirk, J. S. & Tang, D. G. Prostate luminal progenitor cells in development and cancer. Trends Cancer 4, 769\u2013783 (2018).","journal-title":"Trends Cancer"},{"key":"2700_CR104","doi-asserted-by":"publisher","first-page":"4960","DOI":"10.1210\/en.2006-0502","volume":"147","author":"C Castilla","year":"2006","unstructured":"Castilla, C. et al. Bcl-xL is overexpressed in hormone-resistant prostate cancer and promotes survival of LNCaP cells via interaction with proapoptotic Bak. Endocrinology 147, 4960\u20134967 (2006).","journal-title":"Endocrinology"},{"key":"2700_CR105","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-60238-x","volume":"16","author":"A Varkaris","year":"2025","unstructured":"Varkaris, A. et al. BH3 mimetics targeting BCL-XL have efficacy in solid tumors with RB1 loss and replication stress. Nat. Commun. 16, 4931 (2025).","journal-title":"Nat. Commun."},{"key":"2700_CR106","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-64042-5","volume":"16","author":"JM Jimenez-Vacas","year":"2025","unstructured":"Jimenez-Vacas, J. M. et al. Elucidating molecularly stratified single agent, and combination, therapeutic strategies targeting MCL1 for lethal prostate cancer. Nat. Commun. 16, 8806 (2025).","journal-title":"Nat. Commun."},{"key":"2700_CR107","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1158\/2767-9764.CRC-25-0096","volume":"5","author":"BC Brim","year":"2025","unstructured":"Brim, B. C. et al. Direct co-targeting of Bcl-xL and Mcl-1 exhibits synergistic effects in AR-V7-expressing CRPC models. Cancer Res. Commun. 5, 1396\u20131408 (2025).","journal-title":"Cancer Res. Commun."},{"key":"2700_CR108","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1158\/2159-8290.CD-18-1151","volume":"9","author":"SW Lok","year":"2019","unstructured":"Lok, S. W. et al. A Phase Ib dose-escalation and expansion study of the BCL2 inhibitor venetoclax combined with tamoxifen in ER and BCL2-positive metastatic breast cancer. Cancer Discov. 9, 354\u2013369 (2019).","journal-title":"Cancer Discov."},{"key":"2700_CR109","doi-asserted-by":"publisher","first-page":"3256","DOI":"10.1158\/1078-0432.CCR-21-3811","volume":"28","author":"GJ Lindeman","year":"2022","unstructured":"Lindeman, G. J. et al. VERONICA: randomized Phase II study of fulvestrant and venetoclax in ER-positive metastatic breast cancer post-CDK4\/6 inhibitors - efficacy, safety, and biomarker results. Clin. Cancer Res. 28, 3256\u20133267 (2022).","journal-title":"Clin. Cancer Res."},{"key":"2700_CR110","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1007\/s12094-022-03070-9","volume":"25","author":"I Ploumaki","year":"2023","unstructured":"Ploumaki, I. et al. Bcl-2 pathway inhibition in solid tumors: a review of clinical trials. Clin. Transl. Oncol. 25, 1554\u20131578 (2023).","journal-title":"Clin. Transl. Oncol."},{"key":"2700_CR111","doi-asserted-by":"publisher","first-page":"3565","DOI":"10.1038\/s41596-023-00881-0","volume":"18","author":"J Windhager","year":"2023","unstructured":"Windhager, J. et al. An end-to-end workflow for multiplexed image processing and analysis. Nat. Protoc. 18, 3565\u20133613 (2023).","journal-title":"Nat. Protoc."},{"key":"2700_CR112","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.ccr.2010.05.026","volume":"18","author":"BS Taylor","year":"2010","unstructured":"Taylor, B. S. et al. Integrative genomic profiling of human prostate cancer. Cancer Cell 18, 11\u201322 (2010).","journal-title":"Cancer Cell"},{"key":"2700_CR113","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).","journal-title":"Genome Biol."},{"key":"2700_CR114","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2009-10-3-r25","volume":"10","author":"B Langmead","year":"2009","unstructured":"Langmead, B., Trapnell, C., Pop, M. & Salzberg, S. L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25 (2009).","journal-title":"Genome Biol."},{"key":"2700_CR115","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137","volume":"9","author":"Y Zhang","year":"2008","unstructured":"Zhang, Y. et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9, R137 (2008).","journal-title":"Genome Biol."},{"key":"2700_CR116","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-45839-z","volume":"9","author":"HM Amemiya","year":"2019","unstructured":"Amemiya, H. M., Kundaje, A. & Boyle, A. P. The ENCODE blacklist: identification of problematic regions of the genome. Sci. Rep. 9, 9354 (2019).","journal-title":"Sci. Rep."},{"key":"2700_CR117","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"MD Robinson","year":"2010","unstructured":"Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139\u2013140 (2010).","journal-title":"Bioinformatics"},{"key":"2700_CR118","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1093\/bib\/bbs017","volume":"14","author":"H Thorvaldsdottir","year":"2013","unstructured":"Thorvaldsdottir, H., Robinson, J. T. & Mesirov, J. P. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief. Bioinform 14, 178\u2013192 (2013).","journal-title":"Brief. Bioinform"},{"key":"2700_CR119","doi-asserted-by":"publisher","first-page":"10","DOI":"10.14806\/ej.17.1.200","volume":"17","author":"M Martin","year":"2011","unstructured":"Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet. J. 17, 10\u201312 (2011).","journal-title":"EMBnet. J."},{"key":"2700_CR120","doi-asserted-by":"publisher","first-page":"2007","DOI":"10.1373\/clinchem.2008.108845","volume":"54","author":"JP Clark","year":"2008","unstructured":"Clark, J. P. et al. Performance of a single assay for both type III and type VI TMPRSS2:ERG fusions in noninvasive prediction of prostate biopsy outcome. Clin. Chem. 54, 2007\u20132017 (2008).","journal-title":"Clin. Chem."}],"container-title":["Signal Transduction and Targeted Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02700-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02700-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02700-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:02:50Z","timestamp":1777651370000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02700-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,1]]},"references-count":120,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2700"],"URL":"https:\/\/doi.org\/10.1038\/s41392-026-02700-w","relation":{},"ISSN":["2059-3635"],"issn-type":[{"value":"2059-3635","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,1]]},"assertion":[{"value":"17 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 February 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"161"}}