Targeting dual signalling pathways in concert with immune checkpoints for the treatment of pancreatic cancer.

ABSTRACT:

Objective

This study exploits the intersection between molecular-targeted therapies and immune-checkpoint inhibition to define new means to treat pancreatic cancer.

Design

Patient-derived cell lines and xenograft models were used to define the response to CDK4/6 and MEK inhibition in the tumour compartment. Impacts relative to immunotherapy were performed using subcutaneous and orthotopic syngeneic models. Single-cell RNA sequencing and multispectral imaging were employed to delineate effects on the immunological milieu in the tumour microenvironment.

Results

We found that combination treatment with MEK and CDK4/6 inhibitors was effective across a broad range of PDX models in delaying tumour progression. These effects were associated with stable cell-cycle arrest, as

SUBMITTER: Knudsen ES 

PROVIDER: S-EPMC7671951 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature