{"entity":{"id":"castration-resistance","kind":"term","name":"Castration-resistant prostate cancer (CRPC)","aka":["hormone-relapsed prostate cancer","hormone-relapsed","hormone relapsed","hormone-refractory prostate cancer"],"tldr":"Prostate cancer that keeps growing even though testosterone has been reduced to castrate levels.","summary":"Defined by PSA or radiographic progression with testosterone <50 ng/dL. Mechanisms: AR amplification and mutations, AR-V7 splice variants, intratumoural androgen synthesis, glucocorticoid receptor bypass, lineage plasticity to neuroendocrine phenotype. Since 2026 the FDA label language 'androgen pathway modulation-naive or -sensitive' replaces 'hormone-sensitive'.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Castration-resistant_prostate_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Castration-resistant_prostate_cancer"},{"label":"NICE NG131: prostate cancer, diagnosis and management (recommendations, including the Cambridge Prognostic Group table at 1.2.15)","url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["ar-signaling"],"terms":["ar-v7","tnm-prostate-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-visakorpi-androgen-receptor-amplification-nat-genet-1995","paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004","paper-quigley-structural-variation-mcrpc-cell-2018","paper-abida-genomic-correlates-outcome-mcrpc-pnas-2019"],"journals":[],"dependsOn":[],"notes":["The NHS calls it something else. NICE NG131 does not use the phrase castration-resistant anywhere in its recommendations; its section is headed 'hormone-relapsed metastatic prostate cancer' and its advice on docetaxel, on genomic biomarker-based treatment and on zoledronic acid is written in those words. Castration-resistant, castration-sensitive, mCRPC and mHSPC are the words of the trials, the drug labels and the American guidelines. They mean the same thing, and a British patient may meet both in the same week from different people.","Read molecularly, castration resistance is androgen receptor reactivation by one of five routes: amplification of the gene (about half of castration-resistant cohorts against 1% of primaries), amplification of an enhancer 624 kb upstream (81% of 101 deeply sequenced metastases), ligand-binding-domain mutation (13.7 to 18.0%), splicing out the ligand-binding domain (AR-V7), and simply raising receptor expression with no genomic change. The exits from receptor dependence, neuroendocrine transformation and the androgen receptor-null, neuroendocrine-null state, are the minority."],"category":"Clinical"},"route":"/terms/castration-resistance/","neighbours":{"cancer":[{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate-nepc","kind":"cancer","name":"Neuroendocrine and small-cell prostate cancer","route":"/cancers/prostate-nepc/"},{"id":"prostate-nmcrpc","kind":"cancer","name":"Non-metastatic castration-resistant prostate cancer","route":"/cancers/prostate-nmcrpc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"pathway":[{"id":"ar-signaling","kind":"pathway","name":"Androgen receptor signalling","route":"/pathways/ar-signaling/"},{"id":"lineage-plasticity-neuroendocrine","kind":"pathway","name":"Lineage plasticity & neuroendocrine transformation","route":"/pathways/lineage-plasticity-neuroendocrine/"}],"term":[{"id":"adt","kind":"term","name":"Androgen deprivation therapy (ADT)","route":"/terms/adt/"},{"id":"arpi","kind":"term","name":"Androgen receptor pathway inhibitor (ARPI)","route":"/terms/arpi/"},{"id":"ar-v7","kind":"term","name":"AR-V7 splice variant","route":"/terms/ar-v7/"},{"id":"bipolar-androgen-therapy","kind":"term","name":"Bipolar androgen therapy (BAT)","route":"/terms/bipolar-androgen-therapy/"},{"id":"mcrpc-mhspc","kind":"term","name":"mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)","route":"/terms/mcrpc-mhspc/"},{"id":"metastasis-free-survival","kind":"term","name":"Metastasis-free survival (MFS)","route":"/terms/metastasis-free-survival/"},{"id":"neuroendocrine-differentiation","kind":"term","name":"Neuroendocrine differentiation in prostate cancer","route":"/terms/neuroendocrine-differentiation/"},{"id":"orchiectomy","kind":"term","name":"Orchiectomy","route":"/terms/orchiectomy/"},{"id":"prostate-uk-drug-approvals","kind":"term","name":"Prostate cancer drugs in England: what NICE recommends, and what it refuses","route":"/terms/prostate-uk-drug-approvals/"},{"id":"prostate-failed-programmes","kind":"term","name":"Prostate cancer programmes that failed, and what each failure taught","route":"/terms/prostate-failed-programmes/"},{"id":"psa-kinetics","kind":"term","name":"PSA kinetics: PSA doubling time and PSA density","route":"/terms/psa-kinetics/"},{"id":"radiographic-progression-free-survival","kind":"term","name":"Radiographic progression-free survival (rPFS)","route":"/terms/radiographic-progression-free-survival/"},{"id":"ttp","kind":"term","name":"Time to progression (TTP) and time to next treatment (TTNT)","route":"/terms/ttp/"},{"id":"tnm-prostate-cancer","kind":"term","name":"TNM staging for prostate cancer, and what changed in the 9th edition","route":"/terms/tnm-prostate-cancer/"},{"id":"prostate-crpc-sequencing","kind":"term","name":"What follows what in castration-resistant prostate cancer","route":"/terms/prostate-crpc-sequencing/"},{"id":"prostate-hrr-eligibility","kind":"term","name":"Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters","route":"/terms/prostate-hrr-eligibility/"}],"paper":[{"id":"paper-abiraterone-acetate-prostate-n-engl-j-med-2013","kind":"paper","name":"Abiraterone in metastatic prostate cancer without previous chemotherapy","route":"/key-papers/paper-abiraterone-acetate-prostate-n-engl-j-med-2013/"},{"id":"paper-scher-affirm-enzalutamide-nejm-2012","kind":"paper","name":"AFFIRM: increased survival with enzalutamide in prostate cancer after chemotherapy","route":"/key-papers/paper-scher-affirm-enzalutamide-nejm-2012/"},{"id":"paper-bluemn-double-negative-prostate-fgf-mapk-cancer-cell-2017","kind":"paper","name":"Androgen receptor pathway-independent prostate cancer is sustained through FGF signalling","route":"/key-papers/paper-bluemn-double-negative-prostate-fgf-mapk-cancer-cell-2017/"},{"id":"paper-antonarakis-ar-v7-resistance-nejm-2014","kind":"paper","name":"AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer","route":"/key-papers/paper-antonarakis-ar-v7-resistance-nejm-2014/"},{"id":"paper-annala-ctdna-resistance-abiraterone-enzalutamide-cancer-discov-2018","kind":"paper","name":"Circulating tumour DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer","route":"/key-papers/paper-annala-ctdna-resistance-abiraterone-enzalutamide-cancer-discov-2018/"},{"id":"paper-aparicio-aggressive-variant-prostate-tumour-suppressors-ccr-2016","kind":"paper","name":"Combined tumour suppressor defects characterise clinically defined aggressive variant prostate cancers","route":"/key-papers/paper-aparicio-aggressive-variant-prostate-tumour-suppressors-ccr-2016/"},{"id":"paper-beltran-nepc-divergent-evolution-nat-med-2016","kind":"paper","name":"Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer","route":"/key-papers/paper-beltran-nepc-divergent-evolution-nat-med-2016/"},{"id":"paper-abida-genomic-correlates-outcome-mcrpc-pnas-2019","kind":"paper","name":"Genomic correlates of clinical outcome in advanced prostate cancer","route":"/key-papers/paper-abida-genomic-correlates-outcome-mcrpc-pnas-2019/"},{"id":"paper-quigley-structural-variation-mcrpc-cell-2018","kind":"paper","name":"Genomic hallmarks and structural variation in metastatic prostate cancer","route":"/key-papers/paper-quigley-structural-variation-mcrpc-cell-2018/"},{"id":"paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020","kind":"paper","name":"Genomics of lethal prostate cancer at diagnosis and castration resistance","route":"/key-papers/paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020/"},{"id":"paper-huggins-hodges-castration-serum-phosphatases-prostate-1941","kind":"paper","name":"Huggins and Hodges 1941: the effect of castration, of oestrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate","route":"/key-papers/paper-huggins-hodges-castration-serum-phosphatases-prostate-1941/"},{"id":"paper-visakorpi-androgen-receptor-amplification-nat-genet-1995","kind":"paper","name":"In vivo amplification of the androgen receptor gene and progression of human prostate cancer","route":"/key-papers/paper-visakorpi-androgen-receptor-amplification-nat-genet-1995/"},{"id":"paper-ipatential150-ipatasertib-abiraterone-pten-lancet-2021","kind":"paper","name":"IPATential150: ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer","route":"/key-papers/paper-ipatential150-ipatasertib-abiraterone-pten-lancet-2021/"},{"id":"paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004","kind":"paper","name":"Molecular determinants of resistance to antiandrogen therapy","route":"/key-papers/paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004/"},{"id":"paper-labrecque-mcrpc-phenotypes-jci-2019","kind":"paper","name":"Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer","route":"/key-papers/paper-labrecque-mcrpc-phenotypes-jci-2019/"},{"id":"paper-taplin-ar-mutation-androgen-independent-prostate-nejm-1995","kind":"paper","name":"Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer","route":"/key-papers/paper-taplin-ar-mutation-androgen-independent-prostate-nejm-1995/"},{"id":"paper-scher-nuclear-arv7-taxane-vs-arsi-jama-oncol-2018","kind":"paper","name":"Nuclear-localised androgen receptor splice variant 7 in circulating tumour cells as a predictive biomarker in castration-resistant prostate cancer","route":"/key-papers/paper-scher-nuclear-arv7-taxane-vs-arsi-jama-oncol-2018/"},{"id":"paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020","kind":"paper","name":"Oncogenic genomic alterations, clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer","route":"/key-papers/paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020/"},{"id":"paper-attard-abiraterone-phase-1-cyp17-jco-2008","kind":"paper","name":"Phase 1 trial of abiraterone acetate confirms that castration-resistant prostate cancer commonly remains hormone driven","route":"/key-papers/paper-attard-abiraterone-phase-1-cyp17-jco-2008/"},{"id":"paper-beer-prevail-enzalutamide-nejm-2014","kind":"paper","name":"PREVAIL: enzalutamide in metastatic prostate cancer before chemotherapy","route":"/key-papers/paper-beer-prevail-enzalutamide-nejm-2014/"},{"id":"paper-prophecy-arv7-validation-jco-2019","kind":"paper","name":"PROPHECY: prospective multicentre validation of androgen receptor splice variant 7 and hormone therapy resistance in high-risk castration-resistant prostate cancer","route":"/key-papers/paper-prophecy-arv7-validation-jco-2019/"},{"id":"paper-epstein-neuroendocrine-prostate-morphologic-classification-ajsp-2014","kind":"paper","name":"Proposed morphologic classification of prostate cancer with neuroendocrine differentiation","route":"/key-papers/paper-epstein-neuroendocrine-prostate-morphologic-classification-ajsp-2014/"},{"id":"paper-ferraldeschi-pten-protein-loss-abiraterone-eur-urol-2015","kind":"paper","name":"PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate","route":"/key-papers/paper-ferraldeschi-pten-protein-loss-abiraterone-eur-urol-2015/"},{"id":"paper-ku-rb1-trp53-lineage-plasticity-science-2017","kind":"paper","name":"Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis and antiandrogen resistance","route":"/key-papers/paper-ku-rb1-trp53-lineage-plasticity-science-2017/"},{"id":"paper-carver-pi3k-ar-reciprocal-feedback-prostate-cancer-cell-2011","kind":"paper","name":"Reciprocal feedback regulation of PI3K and androgen receptor signalling in PTEN-deficient prostate cancer","route":"/key-papers/paper-carver-pi3k-ar-reciprocal-feedback-prostate-cancer-cell-2011/"},{"id":"paper-teply-restore-bipolar-androgen-therapy-lancet-oncol-2018","kind":"paper","name":"RESTORE: bipolar androgen therapy after progression on enzalutamide in metastatic castration-resistant prostate cancer","route":"/key-papers/paper-teply-restore-bipolar-androgen-therapy-lancet-oncol-2018/"},{"id":"paper-mu-sox2-lineage-plasticity-science-2017","kind":"paper","name":"SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer","route":"/key-papers/paper-mu-sox2-lineage-plasticity-science-2017/"},{"id":"paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015","kind":"paper","name":"SU2C-PCF: integrative clinical genomics of advanced prostate cancer","route":"/key-papers/paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015/"},{"id":"paper-kumar-interindividual-genomic-diversity-metastatic-prostate-nat-med-2016","kind":"paper","name":"Substantial interindividual and limited intraindividual genomic diversity among tumours from men with metastatic prostate cancer","route":"/key-papers/paper-kumar-interindividual-genomic-diversity-metastatic-prostate-nat-med-2016/"},{"id":"paper-petrylak-swog-9916-docetaxel-estramustine-nejm-2004","kind":"paper","name":"SWOG 9916: docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer","route":"/key-papers/paper-petrylak-swog-9916-docetaxel-estramustine-nejm-2004/"},{"id":"paper-tannock-tax-327-docetaxel-prednisone-nejm-2004","kind":"paper","name":"TAX 327: docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer","route":"/key-papers/paper-tannock-tax-327-docetaxel-prednisone-nejm-2004/"},{"id":"paper-grasso-mutational-landscape-lethal-crpc-nature-2012","kind":"paper","name":"The mutational landscape of lethal castration-resistant prostate cancer","route":"/key-papers/paper-grasso-mutational-landscape-lethal-crpc-nature-2012/"},{"id":"paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021","kind":"paper","name":"TRANSFORMER: bipolar androgen therapy versus enzalutamide in asymptomatic metastatic castration-resistant prostate cancer","route":"/key-papers/paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021/"},{"id":"paper-de-bono-tropic-cabazitaxel-lancet-2010","kind":"paper","name":"TROPIC: prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel","route":"/key-papers/paper-de-bono-tropic-cabazitaxel-lancet-2010/"}],"trial":[{"id":"tasquinimod-10tasq10","kind":"trial","name":"10TASQ10","route":"/trials/tasquinimod-10tasq10/"},{"id":"affinity-custirsen","kind":"trial","name":"AFFINITY","route":"/trials/affinity-custirsen/"},{"id":"affirm","kind":"trial","name":"AFFIRM","route":"/trials/affirm/"},{"id":"armor3-sv","kind":"trial","name":"ARMOR3-SV","route":"/trials/armor3-sv/"},{"id":"ca184-043-ipilimumab","kind":"trial","name":"CA184-043","route":"/trials/ca184-043-ipilimumab/"},{"id":"calgb-90401","kind":"trial","name":"CALGB 90401","route":"/trials/calgb-90401/"},{"id":"card","kind":"trial","name":"CARD","route":"/trials/card/"},{"id":"comet-1","kind":"trial","name":"COMET-1","route":"/trials/comet-1/"},{"id":"cou-aa-301","kind":"trial","name":"COU-AA-301","route":"/trials/cou-aa-301/"},{"id":"cou-aa-302","kind":"trial","name":"COU-AA-302","route":"/trials/cou-aa-302/"},{"id":"elm-pc-4-orteronel","kind":"trial","name":"ELM-PC 4","route":"/trials/elm-pc-4-orteronel/"},{"id":"enthuse-m1-zibotentan","kind":"trial","name":"ENTHUSE M1","route":"/trials/enthuse-m1-zibotentan/"},{"id":"era-223","kind":"trial","name":"ERA 223","route":"/trials/era-223/"},{"id":"firstana","kind":"trial","name":"FIRSTANA","route":"/trials/firstana/"},{"id":"hero","kind":"trial","name":"HERO","route":"/trials/hero/"},{"id":"imbassador250","kind":"trial","name":"IMbassador250","route":"/trials/imbassador250/"},{"id":"impact-sipuleucel-t","kind":"trial","name":"IMPACT (sipuleucel-T)","route":"/trials/impact-sipuleucel-t/"},{"id":"keynote-641","kind":"trial","name":"KEYNOTE-641","route":"/trials/keynote-641/"},{"id":"keynote-921","kind":"trial","name":"KEYNOTE-921","route":"/trials/keynote-921/"},{"id":"peace-3","kind":"trial","name":"PEACE-3 (EORTC 1333)","route":"/trials/peace-3/"},{"id":"prevail","kind":"trial","name":"PREVAIL","route":"/trials/prevail/"},{"id":"proselica","kind":"trial","name":"PROSELICA","route":"/trials/proselica/"},{"id":"prospect-prostvac","kind":"trial","name":"PROSPECT","route":"/trials/prospect-prostvac/"},{"id":"psmaddition","kind":"trial","name":"PSMAddition","route":"/trials/psmaddition/"},{"id":"ready-dasatinib","kind":"trial","name":"READY","route":"/trials/ready-dasatinib/"},{"id":"swog-9916","kind":"trial","name":"SWOG 9916","route":"/trials/swog-9916/"},{"id":"swog-s0421-atrasentan","kind":"trial","name":"SWOG S0421","route":"/trials/swog-s0421-atrasentan/"},{"id":"synergy-custirsen","kind":"trial","name":"SYNERGY","route":"/trials/synergy-custirsen/"},{"id":"tax-327","kind":"trial","name":"TAX 327","route":"/trials/tax-327/"},{"id":"triton3","kind":"trial","name":"TRITON3","route":"/trials/triton3/"},{"id":"tropic","kind":"trial","name":"TROPIC","route":"/trials/tropic/"}],"idea":[{"id":"idea-prostate-bipolar-androgen-therapy-phase-3-on-pfs2","kind":"idea","name":"Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint","route":"/ideas/idea-prostate-bipolar-androgen-therapy-phase-3-on-pfs2/"},{"id":"idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine","kind":"idea","name":"Watch for the cancer changing cell type before the biopsy says neuroendocrine, and act on it","route":"/ideas/idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine/"}],"drug":[{"id":"atrasentan","kind":"drug","name":"Atrasentan","route":"/drugs/atrasentan/"},{"id":"custirsen","kind":"drug","name":"Custirsen","route":"/drugs/custirsen/"},{"id":"galeterone","kind":"drug","name":"Galeterone","route":"/drugs/galeterone/"},{"id":"leuprolide","kind":"drug","name":"Leuprolide (leuprorelin) and GnRH agonists","route":"/drugs/leuprolide/"},{"id":"orteronel","kind":"drug","name":"Orteronel","route":"/drugs/orteronel/"},{"id":"prostvac","kind":"drug","name":"PROSTVAC","route":"/drugs/prostvac/"},{"id":"tasquinimod","kind":"drug","name":"Tasquinimod","route":"/drugs/tasquinimod/"},{"id":"zibotentan","kind":"drug","name":"Zibotentan","route":"/drugs/zibotentan/"}],"biomarker":[{"id":"ar-amplification","kind":"biomarker","name":"AR amplification (gene and upstream enhancer)","route":"/biomarkers/ar-amplification/"},{"id":"ar-ligand-binding-domain-mutation","kind":"biomarker","name":"AR ligand-binding-domain mutation (L702H, W742C, H875Y, T878A, F877L)","route":"/biomarkers/ar-ligand-binding-domain-mutation/"},{"id":"hrr-gene-mutation","kind":"biomarker","name":"Homologous recombination repair gene mutation in prostate cancer","route":"/biomarkers/hrr-gene-mutation/"},{"id":"spop-mutation","kind":"biomarker","name":"SPOP mutation","route":"/biomarkers/spop-mutation/"},{"id":"nepc-transformation","kind":"biomarker","name":"Treatment-emergent neuroendocrine transformation (recognising it)","route":"/biomarkers/nepc-transformation/"}],"target":[{"id":"cyp17a1","kind":"target","name":"CYP17A1 (17-alpha-hydroxylase/17,20-lyase)","route":"/targets/cyp17a1/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"}],"collection":[{"id":"prostate-cancer-foundation","kind":"collection","name":"Prostate Cancer Foundation (PCF)","route":"/collections/prostate-cancer-foundation/"}]}}