Anti-angiogenic therapy using the multi-tyrosine kinase inhibitor Regorafenib enhances tumor progression in a transgenic mouse model of ß-cell carcinogenesis.

ABSTRACT:

Background

Pancreatic neuroendocrine tumors (PNETs) represent a distinct hypervascularized tumor entity, often diagnosed at metastatic stage. Therapeutic efficacy of anti-angiogenic multi-kinase inhibitors is frequently limited by primary or acquired resistance in vivo. This study aimed to characterize the molecular mode of action as well as resistance mechanisms to the anti-angiogenic multi-tyrosine kinase inhibitor (TKI) Regorafenib in vitro and in vivo.

Methods

In vitro, human and murine pancreatic neuroendocrine cell lines were comparatively treated with Regorafenib and other TKIs clinically used in PNETs. Effects on cell viability and proliferation were analyzed. In vivo, transgenic RIP1Tag2 mice were treated with Regorafenib at two different time periods during carcino

SUBMITTER: Egidi MJ 

PROVIDER: S-EPMC10575939 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature