New Mechanisms of Resistance to MEK Inhibitors in Melanoma Revealed by Intravital Imaging.

ABSTRACT: Targeted therapeutics that are initially effective in cancer patients nearly invariably engender resistance at some stage, an inherent challenge in the use of any molecular-targeted drug in cancer settings. In this study, we evaluated resistance mechanisms arising in metastatic melanoma to MAPK pathway kinase inhibitors as a strategy to identify candidate strategies to limit risks of resistance. To investigate longitudinal responses, we developed an intravital serial imaging approach that can directly visualize drug response in an inducible RAF-driven, autochthonous murine model of melanoma incorporating a fluorescent reporter allele (tdTomatoLSL). Using this system, we visualized formation and progression of tumors in situ, starting from the single-cell level longitudinally over ti

SUBMITTER: Brighton HE 

PROVIDER: S-EPMC6132242 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature