Network-driven cancer cell avatars for combination discovery and biomarker identification for DNA damage response inhibitors.

ABSTRACT: Combination therapy is well established as a key intervention strategy for cancer treatment, with the potential to overcome monotherapy resistance and deliver a more durable efficacy. However, given the scale of unexplored potential target space and the resulting combinatorial explosion, identifying efficacious drug combinations is a critical unmet need that is still evolving. In this paper, we demonstrate a network biology-driven, simulation-based solution, the Simulated Cell™. Integration of omics data with a curated signaling network enables the accurate and interpretable prediction of 66,348 combination-cell line pairs obtained from a large-scale combinatorial drug sensitivity screen of 684 combinations across 97 cancer cell lines (BAC = 0.62, AUC = 0.7). We highlight drug combination

SUBMITTER: Papp O 

PROVIDER: S-EPMC11192759 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature