Beyond PSMA: theranostic cell surface targets in metastatic prostate cancer.

BACKGROUND: Despite advancements in treatment, metastatic prostate cancer remains a lethal disease. As prostate cancer becomes resistant to standard of care treatments like androgen receptor pathway inhibitors (ARPIs) and chemotherapy, cell surface tumor antigens and receptors become increasingly heterogeneous and diverse, dependent on androgen receptor dependency with relevance for both diagnostic positron emission tomography (PET) imaging and cell surface targeting therapeutics. Our review aims to describe emerging theranostic targets and agents in cell surface imaging and therapies. METHODS: A literature search was carried out in March 2025, on Pubmed, as well as Clinicaltrials.gov to determine cell surface targets with viable trials for imaging and/or therapeutic agents. Keyword searches included "Prostate Cancer" AND "CRPC" AND "Cell Surface Targets." RESULTS: Among the literature, 13 novel targets with robust supporting literature were found. Targets were subsequently divided into targets of interest in AR-positive and AR-negative (NEPC and/or double negative) mCRPC. Ongoing and completed trials for imaging and/or therapeutics leveraging these targets was described. CONCLUSION: Numerous prostate cancer cell surface markers are emerging as theranostic targets. For patients ineligible for or developing progression following PSMA-targeting therapies, extending cell surface targeting therapeutics, whether they are ADCs, cellular therapies, or RPTs, is increasingly vital.

Duke Scholars

Author Andrew John Armstrong Medicine, Medical Oncology