Ribociclib enhances infigratinib-induced cancer cell differentiation and delays resistance in FGFR-driven hepatocellular carcinoma.

ABSTRACT:

Background & aims

Infigratinib is a pan-FGFR (fibroblast growth factor receptor) inhibitor that has shown encouraging activity in FGFR-dependent hepatocellular carcinoma (HCC) models. However, long-term treatment results in the emergence of resistant colonies. We sought to understand the mechanisms behind infigratinib-induced tumour cell differentiation and resistance and to explore the potential of adding the CDK4/6 inhibitor ribociclib to prolong cell differentiation.

Methods

Nine high and three low FGFR1-3-expressing HCC patient-derived xenograft (PDX) tumours were subcutaneously implanted into SCID mice and subsequently treated with either infigratinib alone or in combination with ribociclib. Tumour tissues were then subjected to immunohistochemistry to assess cell diffe

SUBMITTER: Prawira A 

PROVIDER: S-EPMC7894323 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature