Post by Ayham Moustafa

Our work on combining androgen receptor pathway inhibitors (ARPIs) with PARP inhibitors in metastatic prostate cancer has now been published in the British Journal of Cancer. In this study, we investigated the biological rationale behind this therapeutic combination, particularly in models with classical homologous recombination repair (HRR) proficiency. Using prostate cancer cell lines, metastatic patient-derived organoids (mPDOs), lymph node metastatic tissue slice cultures, HRDetect, proteomics, and additional multi-omics analyses, we found that androgen receptor pathway inhibitors can induce a BRCAness-like phenotype through RAD51 downregulation. This impairs DNA double-strand break repair and increases sensitivity to PARP inhibition. Together, these results may help explain why ARPI–PARP inhibitor combinations can be effective beyond classical HRR-deficient prostate cancer. Special thanks to Mohamed Elsesy, Ph.D. & Wael Mansour and many thanks to all coauthors and collaborators for their contributions. Article: https://lnkd.in/eag6xPt5 #ProstateCancer #PrecisionMedicine #PARPInhibitors #AndrogenReceptor #BRCAness #DNARepair #MultiOmics #Proteomics #CancerResearch #Oncology