Targeting BET Proteins Downregulates miR-33a To Promote Synergy with PIM Inhibitors in CMML.

ABSTRACT:

Purpose

Preclinical studies in myeloid neoplasms have demonstrated efficacy of bromodomain and extra-terminal protein inhibitors (BETi). However, BETi demonstrates poor single-agent activity in clinical trials. Several studies suggest that combination with other anticancer inhibitors may enhance the efficacy of BETi.

Experimental design

To nominate BETi combination therapies for myeloid neoplasms, we used a chemical screen with therapies currently in clinical cancer development and validated this screen using a panel of myeloid cell line, heterotopic cell line models, and patient-derived xenograft models of disease. We used standard protein and RNA assays to determine the mechanism responsible for synergy in our disease models.

Results

We identified PIM inhibitors (PI

SUBMITTER: Letson CT 

PROVIDER: S-EPMC10524644 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature