Effective drug combinations in breast, colon and pancreatic cancer cells

• DOI: 10.1038/s41586-022-04437-2
• Publication Date: 2022-02-23T17:04:19Z
• Authors: Patricia Jaaks; Elizabeth A. Coker; Daniel J. Vis; Olivia Edwards; Emma F. Carpenter; Simonetta M. Leto; Lisa Dwane; Francesco Sassi; Howard Lightfoot; Syd Barthorpe; Dieudonne van der...; Wanjuan Yang; Alexandra Beck; Tatiana Mironenko; Caitlin Hall; James Hall; Iman Mali; Laura Richardson; Charlotte Tolley; James Morris; Frances Thomas; Ermira Lleshi; Nanne Aben; Cyril H. Benes; Andrea Bertotti; Livio Trusolino; Lodewyk Wessels; Mathew J. Garnett
• Keywords: Pancreatic Neoplasms; Proto-Oncogene Proteins p21(ras); Drug Combinations; Cell Line, Tumor; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; 610; Humans; Antineoplastic Agents; Drug Synergism; Article; Cell Proliferation; 3. Good health

Abstract Combinations of anti-cancer drugs can overcome resistance and provide new treatments 1,2 . The number possible drug combinations vastly exceeds what could be tested clinically. Efforts to systematically identify active the tissues molecular contexts in which they are most effective accelerate development combination treatments. Here we evaluate potency efficacy 2,025 clinically relevant two-drug combinations, generating a dataset encompassing 125 molecularly characterized breast, colorectal pancreatic cancer cell lines. We show that synergy between is rare highly context-dependent, targeted agents likely synergistic. incorporate multi-omic features biomarkers specify synergistic their contexts, including basal-like breast cancer, microsatellite-stable or KRAS -mutant colon cancer. Our results irinotecan CHEK1 inhibition have effects – TP53 double-mutant cells, leading apoptosis suppression tumour xenograft growth. This study identifies distinct subpopulations resource guide rational efforts develop combinatorial