Targeting MYC effector functions in pancreatic cancer by inhibiting the ATPase RUVBL1/2.

ABSTRACT:

Objective

The hallmark oncogene MYC drives the progression of most tumours, but direct inhibition of MYC by a small-molecule drug has not reached clinical testing. MYC is a transcription factor that depends on several binding partners to function. We therefore explored the possibility of targeting MYC via its interactome in pancreatic ductal adenocarcinoma (PDAC).

Design

To identify the most suitable targets among all MYC binding partners, we constructed a targeted shRNA library and performed screens in cultured PDAC cells and tumours in mice.

Results

Unexpectedly, many MYC binding partners were found to be important for cultured PDAC cells but dispensable in vivo. However, some were also essential for tumours in their natural environment and, among these, the ATPases

SUBMITTER: Vogt M 

PROVIDER: S-EPMC11347226 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature