Leveraging transcriptional dynamics to improve BRAF inhibitor responses in melanoma.

ABSTRACT:

Background

Melanoma is a heterogeneous tumour, but the impact of this heterogeneity upon therapeutic response is not well understood.

Methods

Single cell mRNA analysis was used to define the transcriptional heterogeneity of melanoma and its dynamic response to BRAF inhibitor therapy and treatment holidays. Discrete transcriptional states were defined in cell lines and melanoma patient specimens that predicted initial sensitivity to BRAF inhibition and the potential for effective re-challenge following resistance. A mathematical model was developed to maintain competition between the drug-sensitive and resistant states, which was validated in vivo.

Findings

Our analyses showed melanoma cell lines and patient specimens to be composed of >3 transcriptionally distinct sta

SUBMITTER: Smalley I 

PROVIDER: S-EPMC6838387 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature