Cobimetinib boosts calreticulin and reshapes immunity in triple-negative

Researchers from Taipei Veterans General Hospital and National Yang Ming Chiao Tung University report that cobimetinib, an approved MEK inhibitor known for advanced melanoma, may do more than block a growth-signaling pathway in triple-negative breast cancer (TNBC). In a study published in the Journal of Molecular Medicine, the team found that cobimetinib can trigger immunogenic cell death (ICD), prompting immune activation against tumor cells. They also reported significant reshaping of the immune landscape in animal models. The paper describes ICD features such as calreticulin exposure, ATP release and HMGB1 liberation, which help recruit and mature dendritic cells and enable antigen presentation to CD8-positive T cells. The study tested cobimetinib in TNBC cell lines, observing reduced viability, increased apoptosis, and rising extracellular ATP, alongside changes measured by Western blotting and flow analysis.