Abstract 1313: Genomic and transcriptomic profiles of primary prostate cancer identify unique targets for therapeutic intervention

Abstract

Abstract The tumor microenvironment and genomic landscape of intermediate and high-risk primary localized prostate cancers are clinically heterogeneous and result in variable treatment response in individuals. Cancer-specific alterations at DNA and RNA level is a critical driver of intra-tumoral heterogeneity that significantly impacts the molecular processes which influence the path of disease progression and outcome. In this study, we have performed genomic and transcriptomic analysis of 267 primary prostate cancer. Our analysis revealed actionable alterations and gene signatures for risk stratification and decision support. Clinically significant variants were detected in DNA repair (HR and Mismatch pathway), PI3/AKT, and TP53 signaling pathways with a strong association with disease progression. Further, single-cell analysis (scRNA-seq) of prostate cancer that progressed to metastasis post-therapy identified the unique tumor and immune cell-clusters. Functional annotation of these clusters and drug repurposing studies revealed novel targets for therapeutic intervention that was validated using organoid cultures. Our studies show that an Integrated analysis using genomic, clinical, and pathological features has the potential to define prostate cancer subtypes or phenotypes associated with poor prognosis. Our approach can advance prostate cancer treatment in patients with adverse clinical features by providing treatment options beyond the standard of care (surgery or radiation) and with better therapeutic benefit. Citation Format: Dimple Chakravarty, Zichen Wang, Michael Rossi, Parita Ratnani, Boris Reva, Dmitry Rykunov, Kamala Bhatt, Vinayak Wagaskar, Rachel Weil, Kristin Beaumont, Michael Beaumont, Avi Maayan, Robert Sebra, Nina Bhardwaj, Sujit S. Nair, Ashutosh K. Tewari. Genomic and transcriptomic profiles of primary prostate cancer identify unique targets for therapeutic intervention [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1313.