system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Antineoplastic Agents, Catalytic Domain, Cell Cycle, Cell Line, Tumor, Cell Proliferation, Cell Separation, Cell Survival, Colonic Neoplasms, Drug Screening Assays, Antitumor, Flow Cytometry, Genes, ras, Genotype, Humans, Models, Genetic, Mutation, Niacinamide, Protein-Serine-Threonine Kinases, Pyrimidines, Signal Transduction, raf Kinases.
user
Does bAY61-3606 affect the viability of colon cancer cells in a genotype-directed manner? Context: K-RAS mutation poses a particularly difficult problem for cancer therapy. Activating mutations in K-RAS are common in cancers of the lung, pancreas, and colon and are associated with poor response to therapy. As such, targeted therapies that abrogate K-RAS-induced oncogenicity would be of tremendous value. We searched for small molecule kinase inhibitors that preferentially affect the growth of colorectal cancer cells expressing mutant K-RAS. The mechanism of action of one inhibitor was explored using chemical and genetic approaches. We identified BAY61-3606 as an inhibitor of proliferation in colorectal cancer cells expressing mutant forms of K-RAS, but not in isogenic cells expressing wild-type K-RAS. In addition to its anti-proliferative effects in mutant cells, BAY61-3606 exhibited a distinct biological property in wild-type cells in that it conferred sensitivity to inhibition of RAF. In this context, BAY61-3606 acted by inhibiting MAP4K2 (GCK), which normally activates NFκβ signaling in wild-type cells in response to inhibition of RAF. As a result of MAP4K2 inhibition, wild-type cells became sensitive to AZ-628, a RAF inhibitor, when also treated with BAY61-3606.
assistant
These studies indicate that BAY61-3606 exerts distinct biological activities in different genetic contexts. Final Decision: yes