OncoLoop: A network-based precision cancer medicine framework

Alessandro Vasciaveo, Columbia University, New York, NY, United States.
Juan Martin Arriaga, Columbia University Irving Medical Center, New York, New York, United States.
Francisca Nunes de Almeida, Columbia University Irving Medical Center, New York, United States.
Min Zou, Columbia University Medical Center, New York, NY, United States.
Eugene F. Douglass, University of Georgia, Athens, GA, United States.
Florencia Picech, Columbia University Irving Medical Center, New York, United States.
Maho Shibata, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States.
Antonio Rodriguez-Calero, University of Bern, Bern, Switzerland.
Simone de Brot, University of Bern, Switzerland.
Antonina Mitrofanova, Rutgers Cancer Institute of New Jersey, NJ., United States.
Chee Wai Chua, Shanghai Jiao Tong University, Shanghai, China.
Charles Karan, Columbia University, New York, NY, United States.
Ronald Realubit, Columbia University Irving Medical Center, New York, NY, United States.
Sergey Pampou, Columbia University Irving Medical Center, United States.
Jaime Y. Kim, Columbia University Irving Medical Center, New York, New York, United States.
Stephanie N. Afari, Columbia University Irving Medical Center, New York, United States.
Timur Mukhammadov, Columbia University Irving Medical Center, New York, New York, United States.
Luca Zanella, Columbia University, New York, NY, United States.
Eva Corey, University of Washington, SEATTLE, WA, United States.
Mariano J. Alvarez, DarwinHealth Inc, New York, NY, United States.
Mark A. Rubin, University of Bern, Bern, Bern, Switzerland.
Michael M. Shen, Columbia University Medical Center, New York, NY, United States.
Andrea Califano, Columbia University, New York, NY, United States.
Cory Abate-Shen, Columbia University Irving Medical Center, New York, NY, United States.

Document Type

Journal Article

Publication Date

11-14-2022

Journal

Cancer discovery

DOI

10.1158/2159-8290.CD-22-0342

Abstract

Prioritizing treatments for individual cancer patients remains challenging, and performing co-clinical studies using patient-derived models in real-time is often unfeasible. To circumvent these challenges, we introduce OncoLoop, a precision medicine framework that predicts drug sensitivity in human tumors and their pre-existing high-fidelity (cognate) model(s) by leveraging drug perturbation profiles. As proof-of-concept, we applied OncoLoop to prostate cancer (PCa) using genetically-engineered mouse models (GEMMs) that recapitulate a broad spectrum of disease states, including castration-resistant, metastatic, and neuroendocrine prostate cancer. Interrogation of human PCa cohorts by Master Regulator (MR) conservation analysis revealed that most advanced PCa patients were represented by at least one cognate GEMM-derived tumor (GEMM-DT). Drugs predicted to invert MR activity in patients and their cognate GEMM-DTs were successfully validated in allograft, syngeneic, and patient-derived xenograft (PDX) models of tumors and metastasis. Furthermore, Oncoloop-predicted drugs enhanced the efficacy of clinically-relevant drugs, namely the PD1 inhibitor, nivolumab, and the AR-inhibitor, enzalutamide.

Department

Anatomy and Regenerative Biology

Link to Full Text

Share

COinS