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

science

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 a variety of resistant subtypes, each potentially with their own 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 admitted the possibility that there are drugs that are effective against only subsets of therapy resistant populations but in combination eliminate a large proportion of the resistant population.

BioRxiv     Apr 25, 2025