Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance.

ABSTRACT: Therapies that target signalling molecules that are mutated in cancers can often have substantial short-term effects, but the emergence of resistant cancer cells is a major barrier to full cures. Resistance can result from secondary mutations, but in other cases there is no clear genetic cause, raising the possibility of non-genetic rare cell variability. Here we show that human melanoma cells can display profound transcriptional variability at the single-cell level that predicts which cells will ultimately resist drug treatment. This variability involves infrequent, semi-coordinated transcription of a number of resistance markers at high levels in a very small percentage of cells. The addition of drug then induces epigenetic reprogramming in these cells, converting the transient transcrip

SUBMITTER: Shaffer SM 

PROVIDER: S-EPMC5542814 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature