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Drug Target Encyclopedia Series (19) —PSMA
Release Time：
2025-12-05 14:23
PSMA (Prostate-Specific Membrane Antigen) is a transmembrane glycoprotein highly expressed in prostate cancer and upregulated in advanced and metastatic disease. Its restricted expression in normal tissues and strong correlation with tumor progression make it a validated biomarker and therapeutic target in prostate oncology.
PSMA is implicated in:
• Prostate cancer (localized, metastatic, and castration-resistant stages)
• Salivary gland and renal cell carcinomas (low-level expression)
Targeting PSMA in therapy:
- Radioligand therapy (RLT) – [¹⁷⁷Lu]Lu-PSMA-617 (Pluvicto) has shown clinical success, improving survival in metastatic castration-resistant prostate cancer (mCRPC).
- Antibody-drug conjugates (ADCs) – Deliver cytotoxic agents selectively to PSMA+ tumor cells.
- CAR-T and CAR-NK cell therapies – Engineered immune cells designed to target PSMA-expressing tumors.
- Bispecific T-cell engagers (BiTEs) – Bring T cells into proximity with PSMA+ cancer cells for targeted killing.
Key challenges:
• Tumor heterogeneity and heterogeneous PSMA expression
• Resistance mechanisms post-radioligand or hormonal therapy
• Managing toxicity to PSMA-expressing normal tissues (e.g., salivary glands, kidneys)
🔬 Ongoing research focuses on optimizing next-generation radiopharmaceuticals, developing dual-target CAR-T therapies, and integrating PSMA-targeted agents with androgen receptor pathway inhibitors for synergistic treatment outcomes.
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