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Life sciences · Review
Drugs · October 31, 2026
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Prostate cancer remains a leading cause of cancer-related mortality in men worldwide. While hormone therapy is effective in the early stages of advanced disease, multimodal approaches are often required as disease progresses, including radiotherapy, hormonal agents and chemotherapy. In metastatic castration-resistant prostate cancer (mCRPC), tumour cells become resistant to hormone therapy, resulting in poor survival outcomes despite systemic treatments. Among emerging therapies, radioligand therapy targeting prostate-specific membrane antigen (PSMA) has shown promise. PSMA is a transmembrane glycoprotein highly expressed in prostate cancer cells, with minimal expression in normal tissues. This selective distribution enables precision targeting and minimises toxicity. The radiotheranostic agent [ 177 Lu]Lu-PSMA-617 combines PSMA-617, a small molecule ligand, with the beta-emitting radioisotope 177 Lutetium. This therapy has demonstrated efficacy in patients with mCRPC who have progressed after androgen receptor pathway inhibitors and taxane-based chemotherapy. Its regulatory approval in the USA, UK and Europe marks a pivotal advancement in prostate cancer management. Clinical trials such as TheraP, VISION and PSMAfore have established the role of [ 177 Lu]Lu-PSMA-617 in mCRPC and its potential additive effects with other anti-tumour therapies are under investigation. Strategies to enhance PSMA expression may further improve therapeutic response. With no relevant drug–drug interaction risk, [ 177 Lu]Lu-PSMA-617 may be safely considered for use in combination with other therapies, a key advantage for frail patients with mCRPC on polypharmacy. Post-treatment management remains a challenge and ongoing research aims to optimise long-term outcomes. This review provides a comprehensive update on [ 177 Lu]Lu-PSMA-617 therapy, from molecular mechanisms to clinical application and outlines future directions in the treatment of advanced prostate cancer.