Loading
The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models.
The targets of this cancer's medicines and the ones linked to it directly.
| Target / alteration | Prevalence | Measure | Source |
|---|---|---|---|
| GRPR (gastrin-releasing peptide receptor) Markwalder and Reubi 1999 (Cancer Res); receptor density was high in carcinoma and PIN and low or absent in normal and hyperplastic prostate | 100% | Receptor autoradiography, GRPR in 30 of 30 invasive prostate carcinomas | PMC |
| Androgen receptor AR-V7 in ~20-40% of mCRPC | >95% | AR-driven at diagnosis | Wikipedia |
| PSMA ~10% PSMA-negative or low | >90% | PSMA PET positivity, metastatic disease | PMC |
| RANK ligand (RANKL) Brown 2001 (Urology); 28 patients studied overall, all bone metastases were RANKL-immunoreactive and the fraction of positive tumour cells was higher in bone metastases than in primaries | 91% | IHC, RANKL in 10 of 11 primary prostate cancer specimens (heterogeneous staining) | doi.org |
| PSMA Immunohistochemistry across a panel of normal and malignant tissues found PSMA in 33 of 35 primary prostate adenocarcinomas, 7 of 8 lymph node metastases and 8 of 18 bone metastases, with detectable expression among normal tissues confined to prostatic epithelium, duodenal mucosa, a subset of proximal renal tubules and a subpopulation of neuroendocrine cells in colonic crypts; all other normal tissues, including cerebral cortex and cerebellum, were undetectable (Silver 1997). In practice the PET equivalent of that figure is the screening yield: 200 of 291 men screened for TheraP were eligible on imaging, 69%, with PSMA-low disease or FDG-positive PSMA-negative sites the reason for exclusion (Hofman 2021). | 80-95% | Cell-surface protein expression, read by PET rather than by sequencing | PMC |
| B7-H3 Castration-resistant disease | 80-90% | IHC, any expression | Wikipedia |
| DLL3 Rare in adenocarcinoma | 70-80% | Neuroendocrine prostate cancer only | Wikipedia |
| ERG cBioPortal structural variants, samples with an ERG rearrangement: 152 of 333, 45.6%, in prad_tcga_pub, which reproduces the 46% the TCGA paper reports; 203 of 494, 41.1%, in prad_tcga_pan_can_atlas_2018; 305 of 1,013, 30.1%, in prad_p1000; 104 of 424, 24.5%, in prad_mcspc_mskcc_2020; 127 of 504, 25.2%, in prad_mskcc_2017; 544 of 2,260, 24.1%, in prostate_msk_2024; 528 of 2,069, 25.5%, in prad_msk_stopsack_2021; 134 of 444, 30.2%, in prad_su2c_2019; 62 of 150, 41.3%, in prad_su2c_2015. TMPRSS2 is the partner in almost all of them: 194 of the 203 TCGA PanCancer events, 305 of 305 in prad_p1000 and 128 of 134 in prad_su2c_2019, with SLC45A3 and NDRG1 supplying the rest. | 25-46% | Gene fusion putting ERG under an androgen-responsive promoter | cBioPortal (TCGA) |
| Androgen receptor cBioPortal high-level amplification: 5 of 489, 1.0%, in prad_tcga_pan_can_atlas_2018; 17 of 424, 4.0%, in prad_mcspc_mskcc_2020; 237 of 2,260, 10.5%, in prostate_msk_2024; 9 of 82, 11.0%, in the patient-contributed mpcproject_broad_2021; 217 of 444, 48.9%, in prad_su2c_2019; 78 of 150, 52.0%, in prad_su2c_2015; 85 of 149, 57.0%, in prad_fhcrc. High-level amplification of Xq11-q13 was found in 7 of 23 tumours recurring on androgen deprivation and none of the pre-treatment specimens from the same men (Visakorpi 1995); the upstream enhancer is amplified in 81% of 101 deeply sequenced castration-resistant genomes (Quigley 2018). | 1-57% | High-level amplification of the gene, and of an upstream enhancer | cBioPortal (TCGA) |
| PTEN cBioPortal deep deletion: 85 of 489, 17.4%, in prad_tcga_pan_can_atlas_2018; 50 of 333, 15.0%, in prad_tcga_pub; 124 of 1,013, 12.2%, in prad_p1000; 61 of 424, 14.4%, in prad_mcspc_mskcc_2020; 262 of 2,260, 11.6%, in prostate_msk_2024; 209 of 1,465, 14.3%, in prad_cdk12_mskcc_2020; 114 of 444, 25.7%, in prad_su2c_2019; 41 of 150, 27.3%, in prad_su2c_2015; 55 of 149, 36.9%, in prad_fhcrc; 25 of 61, 41.0%, in prad_mich. Inactivating mutation adds 3 to 11% on top (182 of 2,260, 8.1%, in prostate_msk_2024; 46 of 424, 10.8%, in prad_mcspc_mskcc_2020). | 12-41% | Deep deletion, and inactivating mutation on top of it | cBioPortal (TCGA) |
| PARP BRCA2 ~8-10% | 20-25% | HRR gene alteration (mCRPC) | cBioPortal (TCGA) |
| TP53 cBioPortal mutation: 16 of 477, 3.4%, in prad_cpcg_2017 and 26 of 313, 8.3%, in prostate_dkfz_2018, both localised whole-genome cohorts; 57 of 494, 11.5%, in prad_tcga_pan_can_atlas_2018; 189 of 1,013, 18.7%, in prad_p1000; 129 of 424, 30.4%, in prad_mcspc_mskcc_2020; 650 of 2,260, 28.8%, in prostate_msk_2024; 163 of 444, 36.7%, in prad_su2c_2019; 58 of 150, 38.7%, in prad_su2c_2015; 57 of 141, 40.4%, in prad_fhcrc; 25 of 61, 41.0%, in prad_mich. Deep deletion adds 2 to 15% depending on cohort. | 3-41% | Inactivating mutation, with deep deletion on top | cBioPortal (TCGA) |
| AKT Higher in mCRPC (~40%) | 15-20% | PTEN loss (pathway activation) | cBioPortal (TCGA) |
| RB1 cBioPortal deep deletion: 46 of 489, 9.4%, in prad_tcga_pan_can_atlas_2018; 41 of 1,013, 4.0%, in prad_p1000; 13 of 424, 3.1%, in prad_mcspc_mskcc_2020; 76 of 2,260, 3.4%, in prostate_msk_2024; 43 of 444, 9.7%, in prad_su2c_2019; 29 of 149, 19.5%, in prad_fhcrc; 14 of 61, 23.0%, in prad_mich. Mutation adds 1.5 to 10% (16 of 444, 3.6%, in prad_su2c_2019; 8 of 114, 7.0%, in nepc_wcm_2016). | 3-23% | Deep deletion, and inactivating mutation | cBioPortal (TCGA) |
| BRCA1 / BRCA2 (HRD) | 8-12% | Germline or somatic BRCA2 (metastatic) | cBioPortal (TCGA) |
| SPOP cBioPortal: 318 of 2,260, 14.1%, in prostate_msk_2024; 260 of 2,069, 12.6%, in prad_msk_stopsack_2021; 166 of 1,465, 11.3%, in prad_cdk12_mskcc_2020; 55 of 494, 11.1%, in prad_tcga_pan_can_atlas_2018 and 37 of 333, 11.1%, in prad_tcga_pub; 14 of 112, 12.5%, in prad_broad; 53 of 424, 12.5%, in prad_mcspc_mskcc_2020; 92 of 1,013, 9.1%, in prad_p1000; 38 of 477, 8.0%, in prad_cpcg_2017; 25 of 444, 5.6%, in prad_su2c_2019; 11 of 65, 16.9%, in prad_eururol_2017. The discovery series put it at 6 to 15% across several independent cohorts (Barbieri 2012). | 6-14% | Missense mutation in the substrate-binding cleft | cBioPortal (TCGA) |
| KMT2C cBioPortal mutation in prostate_msk_2024: KMT2C 156 of 2,260, 6.9%; KMT2D 152, 6.7%; KDM6A 81, 3.6%. In prad_su2c_2019: KMT2C 40 of 444, 9.0%; KMT2D 37, 8.3%; KDM6A 11, 2.5%. In prad_su2c_2015: KMT2C 23 of 150, 15.3%; KMT2D 18, 12.0%. KMT2D (then called MLL2) was mutated in 8.6% of the prostate cancers in the rapid-autopsy series, where the MLL complex was shown to interact with the androgen receptor and to be required for receptor-mediated signalling (Grasso 2012). | 4-15% | Truncating mutation in chromatin and histone modifiers | cBioPortal (TCGA) |
| Androgen receptor cBioPortal samples with any AR mutation: 61 of 444, 13.7%, in prad_su2c_2019; 27 of 150, 18.0%, in prad_su2c_2015; 93 of 2,260, 4.1%, in prostate_msk_2024; 9 of 424, 2.1%, in prad_mcspc_mskcc_2020; 2 of 494, 0.4%, in prad_tcga_pan_can_atlas_2018. Allele records in prad_su2c_2019, 72 records: L702H 17, T878A 15, H875Y 11, W742C 8, W742L 4, F877L 3. | 0.4-18% | L702H, W742C/L, H875Y, T878A, F877L | cBioPortal (TCGA) |
| FOXA1 cBioPortal mutation: 351 of 2,260, 15.5%, in prostate_msk_2024; 273 of 2,069, 13.2%, in prad_msk_stopsack_2021; 179 of 1,465, 12.2%, in prad_cdk12_mskcc_2020; 58 of 504, 11.5%, in prad_mskcc_2017; 50 of 424, 11.8%, in prad_mcspc_mskcc_2020; 69 of 1,013, 6.8%, in prad_p1000; 41 of 444, 9.2%, in prad_su2c_2019; 28 of 494, 5.7%, in prad_tcga_pan_can_atlas_2018; 11 of 477, 2.3%, in prad_cpcg_2017. Amplification adds 54 of 2,260 (2.4%) in prostate_msk_2024 and 21 of 149 (14.1%) in prad_fhcrc. It was first described as recurrent in 5 of 147 prostate cancers, 3.4%, across untreated and castration-resistant disease, where the mutant protein repressed androgen signalling and increased tumour growth (Grasso 2012). | 2-16% | Mutation clustered in the forkhead domain, plus amplification | cBioPortal (TCGA) |
| NKX3-1 cBioPortal deep deletion: 53 of 333, 15.9%, in prad_tcga_pub; 39 of 489, 8.0%, in prad_tcga_pan_can_atlas_2018; 44 of 1,013, 4.3%, in prad_p1000; 12 of 424, 2.8%, in prad_mcspc_mskcc_2020; 61 of 2,260, 2.7%, in prostate_msk_2024; 11 of 444, 2.5%, in prad_su2c_2019; 8 of 61, 13.1%, in prad_mich. | 2-16% | Deep deletion (8p21) | cBioPortal (TCGA) |
| ETV1 cBioPortal, samples: in prad_tcga_pub, ETV1 29 of 333 (8.7%), ETV4 16 (4.8%) and FLI1 4 (1.2%), matching the TCGA paper's 8%, 4% and 1%; in prad_tcga_pan_can_atlas_2018, ETV1 11, ETV4 12 and ETV5 2 of 494; in prad_p1000, ETV1 45, ETV4 23 and FLI1 5 of 1,013; in prad_su2c_2019, ETV1 22, ETV4 12, ETV5 3 and FLI1 1 of 444. Counting any ETS fusion together: 224 of 494, 45.3%, in prad_tcga_pan_can_atlas_2018; 378 of 1,013, 37.3%, in prad_p1000; 172 of 444, 38.7%, in prad_su2c_2019; 564 of 2,260, 25.0%, in prostate_msk_2024. | 1-14% | Fusion of a non-ERG ETS transcription factor, usually to TMPRSS2 or SLC45A3 | cBioPortal (TCGA) |
| ATM cBioPortal mutation: 20 of 494, 4.0%, in prad_tcga_pan_can_atlas_2018; 8 of 477, 1.7%, in prad_cpcg_2017; 38 of 1,013, 3.8%, in prad_p1000; 24 of 424, 5.7%, in prad_mcspc_mskcc_2020; 96 of 2,260, 4.2%, in prostate_msk_2024; 27 of 444, 6.1%, in prad_su2c_2019; 16 of 141, 11.3%, in prad_fhcrc. Germline: 11 of 692 men with metastatic disease, 1.6% (Pritchard 2016). | 3-11% | Inactivating mutation, germline or somatic | cBioPortal (TCGA) |
| BRCA1 / BRCA2 (HRD) cBioPortal mutation: 8 of 494, 1.6%, in prad_tcga_pan_can_atlas_2018; 29 of 1,013, 2.9%, in prad_p1000; 19 of 424, 4.5%, in prad_mcspc_mskcc_2020; 91 of 2,260, 4.0%, in prostate_msk_2024; 37 of 444, 8.3%, in prad_su2c_2019; 10 of 150, 6.7%, in prad_su2c_2015. Deep deletion adds 2.2 to 11.5% (17 of 489, 3.5%, in prad_tcga_pan_can_atlas_2018; 13 of 444, 2.9%, in prad_su2c_2019; 7 of 61, 11.5%, in prad_mich). Germline: 37 of 692 men with metastatic disease unselected for family history, 5.3% (Pritchard 2016). | 3-11% | Inactivating mutation, germline or somatic, plus deep deletion | cBioPortal (TCGA) |
| APC cBioPortal mutation: CTNNB1 89 of 2,260, 3.9%, in prostate_msk_2024; 23 of 424, 5.4%, in prad_mcspc_mskcc_2020; 19 of 444, 4.3%, in prad_su2c_2019; 11 of 494, 2.2%, in prad_tcga_pan_can_atlas_2018. APC mutation 176 of 2,260, 7.8%, in prostate_msk_2024; 36 of 424, 8.5%, in prad_mcspc_mskcc_2020; 31 of 444, 7.0%, in prad_su2c_2019, with deep deletion adding 1 to 10%. The CTNNB1 records cluster on the degron: in prostate_msk_2024, S37F 9, T41A 9, D32Y 7, T41I 7, S45P 6 of 94 records. | 2-10% | Activating CTNNB1 exon 3 mutation, or APC inactivation | cBioPortal (TCGA) |
| PIK3CA / PI3K-alpha cBioPortal mutation: PIK3CA 110 of 2,260, 4.9%, in prostate_msk_2024; 24 of 424, 5.7%, in prad_mcspc_mskcc_2020; 14 of 444, 3.2%, in prad_su2c_2019; 10 of 494, 2.0%, in prad_tcga_pan_can_atlas_2018. PIK3CB mutation 31 of 2,260, 1.4%, with amplification 17; AKT1 mutation 42 of 2,260, 1.9%. PIK3CA hotspot records in prostate_msk_2024: E545K 18, E542K 16, H1047R 12 of 116 records. The TCGA taxonomy paper counted a presumed actionable lesion in the PI3K or MAPK pathways in 25% of 333 primary tumours once PTEN was included (Cancer Genome Atlas Research Network 2015). | 2-9% | Activating mutation, plus amplification of PIK3CA or PIK3CB | cBioPortal (TCGA) |
| ZBTB16 cBioPortal ZBTB16 deep deletion: 43 of 1,013, 4.2%, in prad_p1000; 17 of 489, 3.5%, in prad_tcga_pan_can_atlas_2018; 13 of 444, 2.9%, in prad_su2c_2019; 8 of 150, 5.3%, in prad_su2c_2015. ZFHX3 mutation: 142 of 2,260, 6.3%, in prostate_msk_2024; 22 of 444, 5.0%, in prad_su2c_2019, with deep deletion 29 of 489, 5.9%, in prad_tcga_pan_can_atlas_2018. | 1-9% | Deletion or truncating mutation | cBioPortal (TCGA) |
| CDK12 cBioPortal mutation: 9 of 494, 1.8%, in prad_tcga_pan_can_atlas_2018; 1 of 477, 0.2%, in prad_cpcg_2017; 33 of 1,013, 3.3%, in prad_p1000; 24 of 424, 5.7%, in prad_mcspc_mskcc_2020; 130 of 2,260, 5.8%, in prostate_msk_2024; 88 of 1,465, 6.0%, in prad_cdk12_mskcc_2020; 26 of 444, 5.9%, in prad_su2c_2019; 6 of 114, 5.3%, in nepc_wcm_2016. | 1-6% | Biallelic inactivating mutation | cBioPortal (TCGA) |
| CDKN1B cBioPortal deep deletion: 20 of 489, 4.1%, in prad_tcga_pan_can_atlas_2018; 22 of 1,013, 2.2%, in prad_p1000; 13 of 424, 3.1%, in prad_mcspc_mskcc_2020; 71 of 2,260, 3.1%, in prostate_msk_2024; 52 of 1,465, 3.5%, in prad_cdk12_mskcc_2020; 13 of 444, 2.9%, in prad_su2c_2019. | 1-4% | Deep deletion | cBioPortal (TCGA) |
| AURKA Overexpression and gene amplification of AURKA and MYCN were found in 40% of neuroendocrine prostate cancers and 5% of adenocarcinomas in a profiling series of 7 neuroendocrine, 30 adenocarcinoma and 5 benign tissues validated by immunohistochemistry and fluorescence in situ hybridisation on 37 neuroendocrine, 169 adenocarcinoma and 22 benign samples (Beltran 2011). cBioPortal high-level amplification: AURKA 18 of 444, 4.1%, in prad_su2c_2019 (where 3q and 20q gains inflate the call); 2 of 2,260, 0.1%, in prostate_msk_2024. MYCN amplification 8 of 444, 1.8%, in prad_su2c_2019 and 5 of 2,260, 0.2%, in prostate_msk_2024. | 0.1-4% | Co-amplification, enriched in neuroendocrine disease | doi.org |
| MSH2 cBioPortal mutation in prostate_msk_2024: MSH2 26 of 2,260 (1.2%), MSH6 27 (1.2%), PMS2 17 (0.8%), MLH1 16 (0.7%); deep deletion adds MSH2 21, MSH6 15. In prad_su2c_2019: MSH2 6 of 444, MSH6 6, MLH1 3. MSH2 protein loss on immunohistochemistry was present in 14 of 1,176 primary adenocarcinomas and small-cell carcinomas, 1.2% (Guedes 2017). | 0.2-3% | MSH2, MSH6, MLH1 or PMS2 inactivation, often by complex rearrangement | cBioPortal (TCGA) |
| BRCA1 / BRCA2 (HRD) cBioPortal mutation: 1 of 494, 0.2%, in prad_tcga_pan_can_atlas_2018; 6 of 1,013, 0.6%, in prad_p1000; 1 of 424, 0.2%, in prad_mcspc_mskcc_2020; 18 of 2,260, 0.8%, in prostate_msk_2024; 8 of 444, 1.8%, in prad_su2c_2019. Germline: 6 of 692, 0.9% (Pritchard 2016). | 0.2-2% | Inactivating mutation, germline or somatic | cBioPortal (TCGA) |
| PALB2 cBioPortal mutation in prostate_msk_2024 (2,260 samples): PALB2 19 (0.8%), CHEK2 14 (0.6%), BRIP1 17 (0.8%), BARD1 10 (0.4%), FANCA 15 (0.7%), RAD51B 6, RAD51C 3, RAD51D 2. Deep deletion adds a little: FANCA 42 of 2,260 (1.9%), CHEK2 5, PALB2 4, RAD51B 5. Germline in 692 men with metastatic disease: CHEK2 10 of 534 men with data, 1.9%; RAD51D 3, 0.4%; PALB2 3, 0.4% (Pritchard 2016). | 0.2-2% | PALB2, CHEK2, RAD51B/C/D, BARD1, BRIP1, FANCA, NBN inactivation | cBioPortal (TCGA) |
| IDH1 / IDH2 cBioPortal: 5 of 494, 1.0%, in prad_tcga_pan_can_atlas_2018 (2 R132C, 1 R132G, 1 R132H); 9 of 1,013, 0.9%, in prad_p1000; 14 of 2,260, 0.6%, in prostate_msk_2024; 3 of 477, 0.6%, in prad_cpcg_2017. The TCGA taxonomy put it at 1% of 333 primary tumours and showed the IDH1-mutant subset carried a methylator phenotype (Cancer Genome Atlas Research Network 2015). | 0.5-1% | Hotspot mutation defining a methylator subtype | cBioPortal (TCGA) |
| 5-alpha-reductase type 2 (SRD5A2) | host% | Host enzyme in normal and malignant prostate; finasteride and dutasteride were tested for prevention, not as a tumour marker | cancer.gov |
| CYP17A1 (17-alpha-hydroxylase/17,20-lyase) | nearly all% | Androgen-driven at diagnosis; abiraterone acts on androgen synthesis in almost every prostate cancer, resistance develops later | cancer.gov |
| EZH2 | n/a | Overexpression in CRPC; no threshold | Wikipedia |
| GnRH receptor (GNRHR) | host% | Host target: pituitary receptor that starts the testosterone chain. Not a tumour alteration, so no prevalence applies; the drug acts on normal tissue or on symptoms. | |
| IMP dehydrogenase (IMPDH2) | host% | Host enzyme in normal and malignant prostate; finasteride and dutasteride were tested for prevention, not as a tumour marker | cancer.gov |
| Prostatic acid phosphatase (ACP3, PAP) | nearly all% | Prostatic acid phosphatase expressed by prostate epithelium and most prostate cancers, the antigen sipuleucel-T targets | cancer.gov |
How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.
7 cell lines, 3 mouse models and 6 repositories are listed for this cancer. See them →