Adaptive chromatin remodeling and transcriptional changes of the functional kinome in tumor cells in response to targeted kinase inhibition.

ABSTRACT: Pharmacological inhibition of protein kinases induces adaptive reprogramming of tumor cell regulatory networks by altering expression of genes that regulate signaling, including protein kinases. Adaptive responses are dependent on transcriptional changes resulting from remodeling of enhancer and promoter landscapes. Enhancer and promoter remodeling in response to targeted kinase inhibition is controlled by changes in open chromatin state and by activity of specific transcription factors, such as c-MYC. This review focuses on the dynamic plasticity of protein kinase expression of the tumor cell kinome and the resulting adaptive resistance to targeted kinase inhibition. Plasticity of the functional kinome has been shown in patient window trials where triple-negative and human epidermal growt

SUBMITTER: East MP 

PROVIDER: S-EPMC8888345 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature