Heterogeneous therapy-resistant cancer cells have distinct and exploitable drug sensitivity profiles.

ABSTRACT: Resistance to targeted therapies is a significant clinical problem, but eliminating resistant cancer cells has proven difficult. One potential reason for this difficulty is heterogeneity in the resistant population: even genetically homogeneous cancer cell populations can give rise to many resistant subtypes, each potentially with specific second-line drug vulnerabilities. Using high-throughput drug screening of genetically-identical resistant clones with varying transcriptomes and morphologies, we show that each clone had a distinct drug sensitivity profile. These results suggested that there are drugs that are effective against only subsets of resistant populations but in combination eliminate a large proportion of the resistant population. Using the individual clone sensitivity profiles

SUBMITTER: Busch GT 

PROVIDER: S-EPMC12247746 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature