trametinib + uprosertib

Trametinib + uprosertib is an investigational combination therapy consisting of two small molecule inhibitors targeting key signaling pathways in cancer. Trametinib is a selective inhibitor of MEK1 and MEK2 (mitogen-activated protein kinase kinases), while uprosertib (GSK2141795) is an oral pan-AKT inhibitor. The rationale for combining these agents stems from the frequent activation of both the MAPK/ERK and PI3K/AKT pathways in various cancers, including triple-negative breast cancer (TNBC) and melanoma. Preclinical studies suggested that dual inhibition could overcome resistance mechanisms seen with single-agent therapies. Clinical trials have evaluated this combination primarily in patients with metastatic TNBC previously treated with chemotherapy and in BRAF-wild type advanced melanoma. However, clinical activity has been limited by poor tolerability—particularly gastrointestinal toxicity—and minimal efficacy at tolerated doses[1][2][6].

Brand names

Mekinist

Other names

trametinib + uprosertib