Drug perturbation RNA sequencing of 2 prostate cancer cell lines

Prioritizing cancer treatments at the individual patient level remains challenging, and performing co-clinical studies using patient-derived models in real-time is often not unfeasible. To circumvent these challenges, we introduce OncoLoop, a precision medicine framework to predict and validate drug sensitivity sensitivity in both a human tumors and in its their pre-existing high est-fidelity (cognate) (cognate) model(s)—for contextual in vivo validation—) by leveraging perturbational profiles of clinically-relevant oncology drugs. As proof-of-concept, we applied OncoLoop to prostate cancer (PCa) using a series of genetically engineered mouse models (GEMMs) that capture the broad spectrum of disease states, including metastatic, castration-resistant, metastatic, and neuroendocrine prostate cancer. Interrogation of published cohorts revealed that most patients were represented by at least one cognate GEMM-derived tumor (GEMM-DT), based on upon Master Regulator (MR) conservation analysis. Drugs recurrently predicted to recurrently invert MR protein activity in patients and their cognate GEMM-DTs were successfully validated, including in two cognate allografts and one cognate patient derived xenograft (PDX). OncoLoop is highly generalizable and can be extended to other cancers and potentially other pathologdiseasesies. Overall design: 1728 RNAseq profiles of perturbed cell-lines with FDA-approved drugs and late-stage experimental compounds. Cell-lines were treated at a 48-hour IC20 for each drug and RNA was collected at 24 hours to minimize cell-death. Samples were prepared and sequences in batches of 96 that included 6 vehicle (DMSO) and 6 water controls. 2 replicates were taken for each drug-cell-line pair.