A protein on prostate cancer cells that lets doctors both see the cancer on a PET scan and hit it with a radioactive drug. This dossier gathers the 6 products (4 approved), 7 trials, 0 pathways and 5 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Biology
PSMA is a type II transmembrane glutamate carboxypeptidase; expression increases with grade and castration resistance. Also expressed in tumour neovasculature of other cancers.
- Prostate cancer (>90%)
- Neovasculature of RCC, glioma, others
Elsewhere: identifiers and databases
Built from HGNC, Ensembl, UniProt and ChEMBL idsHow common it is, by cancer
Full matrix →| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Prostate cancer | >90% | PSMA PET positivity, metastatic disease | ~10% PSMA-negative or low | PMC |
| Renal cell carcinoma | 60-80% | Neovascular PSMA expression | Clear-cell; imaging studies | PMC |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Products by modality and phase
Browse products →| Modality | Approved | Phase 3 |
|---|---|---|
| Imaging agent 3 | — | |
| Radiopharmaceutical 3 |
Trials
Evidence ranking →| Trial | Phase | Status | Setting | Result | Products |
|---|---|---|---|---|---|
| ECLIPSE NCT05204927 | 3 | Positive | PSMA-positive mCRPC after ARPI, taxane-naive: 177Lu-PSMA-I&T (7.4 GBq × 6) vs ARPI switch | rPFS significantly improved. | |
| PSMAddition NCT04720157 | 3 | Positive | PSMA-positive metastatic hormone-sensitive prostate cancer: 177Lu-PSMA-617 + ADT + ARPI vs ADT + ARPI | rPFS HR 0.72 (updated 0.67); OS HR 0.80 (NS, immature). | |
| SPLASH NCT04647526 | 3 | Mixed | PSMA-positive mCRPC after one ARPI, taxane-naive: 177Lu-PNT2002 vs ARPI switch | rPFS HR 0.71; interim OS HR 1.11. | |
| PSMAfore NCT04689828 | 3 | Positive | PSMA+ mCRPC after one ARPI, taxane-naive: 177Lu-PSMA-617 vs ARPI switch | rPFS HR 0.41. | |
| VISION NCT03511664 | 3 | Positive | PSMA+ metastatic castration-resistant prostate cancer after ARPI and taxane: 177Lu-PSMA-617 + SOC vs SOC | OS HR 0.62. | |
| AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617) NCT06402331 | 3 | Recruiting | PSMA-positive mCRPC: actinium-225 PSMA radioligands vs standard of care, including after 177Lu-PSMA | ||
| TheraP (ANZUP 1603) NCT03392428 | 2 | Positive | mCRPC after docetaxel: 177Lu-PSMA-617 vs cabazitaxel, PSMA PET/FDG PET selected | PSA50 66% vs 37%; OS HR 0.97. |
Resistance routes that involve this target
Unaddressed routes →More receptor, or mutations (F877L, T878A) that turn antagonists into agonists.
- AR degraders and N-terminal-domain inhibitors (trials); PSMA radioligand therapy
Truncated receptor lacking the ligand-binding domain is constitutively active and invisible to enzalutamide.
- Taxanes retain activity; N-terminal-domain inhibitors
RB1/TP53 loss enables transdifferentiation; AR-indifferent, DLL3-positive, PSMA-negative.
- Platinum-etoposide; DLL3 engagers (tarlatamab) and B7-H3 ADCs in trials
Reciprocal feedback between AR and PI3K pathways.
- Capivasertib + abiraterone (approved 2026 for PTEN-deficient disease)
GR drives an AR-like transcriptional programme under enzalutamide.
- GR antagonists (relacorilant tested in prostate cancer)
Pathways where it is a node
Pathway-to-drug matrix →No pathway diagram carries this target as a node.
Companion diagnostics and assays
Assay registry →| Assay | Platform | Cut-off | Gates |
|---|---|---|---|
| PSMA PET (Ga-68 PSMA-11, F-18 piflufolastat, F-18 flotufolastat) Novartis, Lantheus, Blue Earth Diagnostics · FDA CDx 2022 | Imaging | At least one PSMA-positive lesion and no dominant PSMA-negative lesion (VISION criteria) for lutetium-177 PSMA-617 |
Preclinical models
All models →| Cell line | Identifiers | Why it is used |
|---|---|---|
| LNCaP | CVCL_0395 | PSMA-high; the radioligand binding and dosimetry standard. |
| C4-2 | CVCL_4782 | PSMA-high, castration-resistant. |
| 22Rv1 | CVCL_1045 · ACH-000956 | Moderate PSMA. |
| PC-3 | CVCL_0035 · ACH-000090 | PSMA-negative control; PC-3 PIP (PSMA-transduced) and PC-3 flu form the classic matched pair. |
| DU145 | CVCL_0105 · ACH-000979 | PSMA-negative. |
Mouse PSMA (Folh1) differs in expression pattern (kidney, not prostate), so off-target dosimetry in mice does not predict human salivary or renal uptake.
Open questions
All open questions →- 01
Should PSMA radioligand therapy move to hormone-sensitive disease, and is an alpha emitter better than lutetium-177?
clinicalindustryWhy unresolved. VISION and PSMAfore established lutetium-177 PSMA-617 late in the disease; PSMAddition tests it in hormone-sensitive disease and actinium-225 programmes report deeper responses with salivary toxicity, but head-to-head data are absent.
What would answer it. Randomised trials of lutetium versus actinium PSMA ligands and of earlier use with overall survival, quality of life and dosimetry.
Source: VISION, NEJM 2021
Ideas and companies
Key papers and the live literature
Preprints →- VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer · New England Journal of Medicine 2021
Query for this target: (TITLE:"PSMA" OR ABSTRACT:"PSMA" OR TITLE:"FOLH1" OR ABSTRACT:"FOLH1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about PSMA, not a curated reading list.
Export
The dossier as machine-readable JSON: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/psma.json. Licence CC BY 4.0.