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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 15 products (6 approved), 36 trials, 1 pathway 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.
PSMA is a type II transmembrane glutamate carboxypeptidase; expression increases with grade and castration resistance. Also expressed in tumour neovasculature of other cancers.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Prostate cancer | >90% | PSMA PET positivity, metastatic disease | ~10% PSMA-negative or low | PMC |
| Prostate cancer | 80-95% | Cell-surface protein expression, read by PET rather than by sequencing | 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). | 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.
| Modality | Approved | Phase 3 | Phase 2 |
|---|---|---|---|
| Imaging agent 7 | - | ||
| Radiopharmaceutical 5 | |||
| Bispecific antibody 1 | - | - | |
| not stated 1 | - | - | |
| Vaccine or virus 1 | - | - |
| Trial | 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 (95% CI 0.58 to 0.90, p=0.0021), medians not reached in either arm at the second interim analysis; overall survival not yet reported. | |
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. | |
PSMA-PreRP NCT03368547 | 3 | Positive | Intermediate- to high-risk prostate cancer considered for radical prostatectomy: a single 68Ga-PSMA-11 PET scan for pelvic nodal staging, read against histopathology after prostatectomy and pelvic lymph node dissection | Per-patient sensitivity 0.40 (95% CI 0.34 to 0.46) and specificity 0.95 (0.92 to 0.97) for pelvic nodal metastasis against histopathology in the 277-man surgery cohort; positive predictive value 0.75, negative predictive value 0.81. | |
VISION NCT03511664 | 3 | Positive | PSMA+ metastatic castration-resistant prostate cancer after ARPI and taxane: 177Lu-PSMA-617 + SOC vs SOC | OS HR 0.62. | |
| 3 | Active | A Multi-center, Open-label, Single Arm Phase III Clinical Trial for the Diagnostic Efficacy Assessment and Safety Evaluation by [18F]Florastamin PET/CT Imaging Examination in Patients With Suspected Recurrent or Metastatic Prostate Cancer | - | ||
| 3 | Recruiting | A Phase III, Randomized, Open-Label, Multicenter Study Comparing HRS-4357 With Novel Androgen Receptor Pathway Inhibitors in Patients With Progressive, PSMA-Positive Metastatic Castration-Resistant Prostate Cancer | - | ||
| 3 | Recruiting | A Phase 3 Randomized, Double-blind, Placebo-controlled Study of Pasritamig (JNJ-78278343), a T Cell Engaging Agent Targeting Human Kallikrein 2, With or Without JNJ-87189401, a PSMA-CD28 Costimulatory Agent, Plus Best Supportive Care Versus Best Supportive Care for Late-line Metastatic Castration-resistant Prostate Cancer | - | ||
| 3 | Recruiting | A Phase III, Multicentre, Randomised Controlled Study to Evaluate the Efficacy and Safety of AZD2265 (FPI-2265) ²²⁵Ac-PSMA-I&T Compared With Standard of Care in Patients With PSMA-positive Metastatic Castration-resistant Prostate Cancer (VECTRA-01) | - | ||
| 3 | Recruiting | Prospective, Multi-Center Study to Assess the Diagnostic Performance of [18F]PSMA-1007 PET/CT Imaging in Patients With Newly-Diagnosed High-Risk or Very-High-Risk Prostate Cancer | - | ||
| 3 | Active | A Multi Center, Non-randomized, Open, Phase 3 Study to Evaluate the Clinical Usefulness of [F-18]Florastamin PET/CT Imaging Diagnosis Compared to MRI Diagnosis in Prostate Cancer Risk Groups | - | ||
| 3 | Recruiting | A Single Arm, Multicenter, Prospective, Open Label, Longitudinal Phase 3 Study of Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) Combined With Magnetic Resonance Imaging (MRI) Compared to Standard of Care (SOC) for the Detection of Prostate Cancer (PCa). | - | ||
| 3 | - | Phase 3 Randomized Trial Of PSMA PET Prior to Definitive Radiation Therapy for Unfavorable Intermediate-Risk or High-Risk Prostate Cancer [PSMA dRT] | - | ||
| 3 | Recruiting | A Phase III, Open-label, Multi-center, Randomized Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive Metastatic Castration Resistant Prostate Cancer | - | ||
| 3 | Completed | A Phase 3, Multi-Center, Open-Label Study to Assess the Diagnostic Performance and Clinical Impact of 18F-DCFPyL PET/CT Imaging Results in Men With Suspected Recurrence of Prostate Cancer | - | ||
| 3 | Recruiting | A Phase III, Prospective, Open-Label, Single-Arm, Multi-center Clinical Study to Assess the Diagnostic Performance and Safety of 18F-Florastamin PET/CT Imaging in Patients With Suspected Recurrence of Prostate Cancer | - | ||
| 2/3 | Recruiting | PSMAcTION: A Phase II/III, Open-label, International, Multicenter, Randomized Study of AAA817 Versus Standard of Care in the Treatment of Adult Participants With PSMA Positive Metastatic Castration-resistant Prostate Cancer Who Progressed on or After [177Lu]Lu-PSMA Targeted Therapy | - | ||
PSMA-PET to Guide Prostatectomy NCT05381103 | 2/3 | Recruiting | PSMA-PET to Guide Prostatectomy: A Randomized Trial | - | - |
| 2/3 | Completed | A PrOspective Phase 2/3 Multi-Center Study of 18F-DCFPyL PET/CT Imaging in Patients With PRostate Cancer: Examination of Diagnostic AccuracY (OSPREY) | - | ||
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. | |
| 2 | Active | PSMA-positive mCRPC: actinium-225 PSMA radioligands vs standard of care, including after 177Lu-PSMA | - | ||
| 2 | Active | A Phase II, Open-label, Multi-Center, Randomized Study of Combination of Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) and Androgen Receptor Pathway Inhibitor (ARPI) vs. Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in First-line Treatment of Patients With Prostate-Specific Membrane Antigen (PSMA)-Positive Progressive Metastatic Castration Resistant Prostate Cancer (mCRPC) | - | ||
| 2 | Recruiting | Assessing the Efficacy of Neoadjuvant Androgen Deprivation Therapy (ADT) Utilizing 18F-Flotufolastat PSMA PET/CT in Patients With High-Risk Localized Prostate Cancer (LHRPC) | - | ||
| 2 | Recruiting | Diagnostic Utility of rhPSMA-7.3 (18F) PET /CT Imaging in Patients With Prostate Cancer on Active Surveillance | - | ||
| 2 | Active | A Phase 2, Open-label, Multi-centre Study of FPI-2265 (225Ac-PSMA-I&T) and Olaparib in Participants With Metastatic Castration Resistant Prostate Cancer (mCRPC) | - | ||
| 2 | Recruiting | RhPSMA-7.3(18F)-PET Scan to Detect Prostate Cancer in Patients with Early PSA Recurrence | - | ||
| 2 | Active | An Open-label Dosimetry, Biodistribution, Tolerability and Safety Study of Lutetium (177Lu) Vipivotide Tetraxetan in Participants With Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC) With Moderately and Severely Impaired and With Normal Renal Function. | - | ||
| 2 | Active | PSMA-directed Targeted Alpha Therapy With FPI-2265 (225Ac-PSMA-I&T) for the Treatment of Metastatic Castration-resISTant Prostate Cancer (TATCIST). A Phase II Clinical Trial. | - | ||
| 1/2 | Recruiting | A Phase 1/2 Dose Escalation Trial With Administration Schedule Exploration Evaluating Single Agent TD001, a PSMA-Targeted Antibody-Drug Conjugate, in Patients With PSMA-Expressing Metastatic Castration-Resistant Prostate Cancer | - | - |
More receptor, or mutations (F877L, T878A) that turn antagonists into agonists.
Truncated receptor lacking the ligand-binding domain is constitutively active and invisible to enzalutamide.
RB1/TP53 loss enables transdifferentiation; AR-indifferent, DLL3-positive, PSMA-negative.
Reciprocal feedback between AR and PI3K pathways.
GR drives an AR-like transcriptional programme under enzalutamide.
KEGG's prostate cancer map centres on the androgen receptor, the hormone switch that prostate cells depend on, plus loss of PTEN and NKX3.1 that lets PI3K/AKT growth signalling run free. Hormone therapy, AR antagonists and now AKT inhibitors act on these two arms.
Which nodes have drugs →| 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 |
| 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.
Why 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.
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.
The dossier as machine-readable JSON, at /api/v1/dossiers/psma.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-NC 4.0.