trametinib + hydroxychloroquine (National Cancer Institute)

This combination therapy consists of **trametinib**, a small molecule inhibitor of MEK1 and MEK2, and **hydroxychloroquine**, an autophagy inhibitor. It is currently being investigated by the National Cancer Institute (NCI) in a Phase 2 clinical trial (NCT04566133) for the treatment of patients with KRAS-mutated refractory biliary tract carcinoma (BTC) who have failed at least one line of chemotherapy. The therapeutic rationale is based on the observation that inhibition of the MAPK pathway via MEK inhibitors can trigger autophagy as a survival mechanism in KRAS-mutant cancer cells. By combining trametinib with hydroxychloroquine, which prevents lysosomal acidification and autophagosome-lysosome fusion, researchers aim to block this resistance pathway and enhance the anti-tumor efficacy of MEK inhibition.

Brand names

MekinistPlaquenil

Other names

trametinib and hydroxychloroquineMEK inhibitor and autophagy inhibitor combination