Drug dependence in cancer is exploitable by optimally constructed treatment holidays.

ABSTRACT: Cancers with acquired resistance to targeted therapy can become simultaneously dependent on the presence of the targeted therapy drug for survival, suggesting that intermittent therapy may slow resistance. However, relatively little is known about which tumours are likely to become dependent and how to schedule intermittent therapy optimally. Here we characterized drug dependence across a panel of over 75 MAPK-inhibitor-resistant BRAF^V600E mutant melanoma models at the population and single-clone levels. Melanocytic differentiated models exhibited a much greater tendency to give rise to drug-dependent progeny than their dedifferentiated counterparts. Mechanistically, acquired loss of microphthalmia-associated transcription factor in differentiated melanoma models drives ERK-JunB

SUBMITTER: Maltas J 

PROVIDER: S-EPMC10918730 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature