Prostate-specific membrane antigen (PSMA) is upregulated in prostate cancer cells relative to other cells. The increased expression and enzymatic activity of PSMA in high-stage disease confers a selective advantage on such cells, contributing to their increased proliferation, the tendency to metastasize and the development of a castration-resistant phenotype.
The decades of radiobiochemical advances in the development of PSMA targeting radiolabelled ligands has led to the subsequent FDA approval of a number of radiotracers and radiotherapeutics for clinical use. Novel developments in therapeutic advances using PSMA-based combinatorial approaches include PSMA-targeted antibody-drug conjugates and PSMA-targeted radionuclide payloads. Combining and sequencing some of these strategies with standard therapy options such as surgery, radiotherapy and androgen receptor pathway inhibitors could improve patient outcomes. Immunotherapy and chimeric antigen receptor T cell therapy are relevant to PSMA-based therapies as PSMA can serve as a specific target antigen for these treatments, enabling precise tumour recognition and enhanced efficacy of prostate cancer therapies.
Nature reviews. Urology. 2025 Nov 10 [Epub ahead of print]
Sola Adeleke, Joao R Galante, Yishen Wang, Gurdip Azad, Simon Wan, Athar Haroon, Diletta Bianchini, Jamshed Bomanji, Michael S Hofman, Travis S Young, Gary J R Cook
School of Biomedical Engineering and Imaging Sciences (BMEIS), King's College London, London, UK. ., Royal Marsden Hospital NHS Foundation Trust, London, UK., Royal Free London NHS Foundation Trust, London, UK., Guy's & St Thomas' NHS Foundation Trust, London, UK., Institute of Nuclear Medicine, University College London, London, UK., St Bartholomew's Hospital NHS Foundation Trust, London, UK., Kent Oncology Centre, Maidstone & Tunbridge Wells Hospitals, Kent, UK., Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC), Molecular Imaging and Therapeutic Nuclear Medicine, Cancer Imaging, Peter MacCallum Centre Melbourne, Melbourne, Victoria, Australia., California Institute for Biomedical Research (CALIBR), Scripps Research, La Jolla, CA, USA., School of Biomedical Engineering and Imaging Sciences (BMEIS), King's College London, London, UK.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/41214335