Modulation of cabozantinib efficacy by the prostate tumor microenvironment.

ABSTRACT: The tumor microenvironment (TME) is increasingly recognized as the arbiter of metastatic progression and drug resistance in advanced prostate cancer (PCa). Cabozantinib is a potent tyrosine kinase inhibitor (TKI) with reported biological activity in the PCa epithelia, but failed to provide an overall survival benefit in phase 3 clinical trials. However, the promising biologic efficacy of the drug in early trials warranted a better understanding of the mechanism of action, with the goal of improving patient selection for TKI-based therapy such as cabozantinib. We found a 100-fold lower cabozantinib IC₅₀ in macrophages, PCa associated fibroblasts, and bone marrow fibroblasts compared to PCa epithelia. In PCa mouse models, pre-treatment with cabozantinib potentiated osseous and vis

SUBMITTER: Tripathi M 

PROVIDER: S-EPMC5675680 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature