Disrupting CDK9 activity suppresses triple-negative breast cancer and is enhanced by EGFR Inhibition.

ABSTRACT:

Purpose

CDK9, in complex with cyclin T1 or T2, is essential for mRNA transcription by enabling paused RNA polymerase II to proceed into elongation. Increasing evidence highlights CDK9's involvement in transcriptional addiction in cancer. Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype for which effective targeted therapies remain limited. Here, we aimed to define the therapeutic potential of novel CDK9 inhibitors in TNBC.

Methods

We explored the efficacy and mechanism of action of novel CDK9 inhibitors, alone or in combination with EGFR inhibitors, using TNBC cell lines and in vivo xenograft models.

Results

Targeting CDK9 significantly impaired proliferation and induced apoptosis in multiple TNBC cell lines. Transcriptomic analyses revealed

SUBMITTER: van der Noord VE 

PROVIDER: S-EPMC12783313 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature