Targeting MEK1/2 with FCN-159: A Promising Oral Therapy for Advanced Solid Tumors

The MEK1/2 enzyme is integral to the RAS/RAF/MEK/ERK pathway, which is involved in a range of cellular activities such as growth, change, movement, life span, and the formation of new blood vessels. Problems with this pathway due to mutations in BRAF, KRAS, and NRAS are common in many cancers, including melanoma, lung cancer, prostate cancer, breast cancer, and leukemias. MEK inhibitors can stop cancer cells from growing and can be a good way to fight cancer.

FCN-159 is a new type of MEK1/2 inhibitor that can be taken by mouth. It works specifically against MEK1 and MEK2 and is very effective at stopping the growth of cancer cells that have mutations in RAS/RAF, while not affecting normal cells. It also stops a protein called ERK from being activated in colon cancer cells, which leads to the cells not dividing and dying.

Tests with FCN-159 on different types of cancer, including those that have spread to other parts of the body, have shown that it can shrink tumors. It also works well in models that mimic real patient tumors with NRAS mutations. The drug seems to work as well as or better than other MEK inhibitors that are already being used.

FCN-159 also has good properties when it comes to how it is absorbed and used by the body, and it appears to be safe. It stays in the system longer and is more effective at the doses tested compared to trametinib, another MEK inhibitor.

Overall, FCN-159 looks promising as a new treatment for cancer. It has shown strong effects in stopping cancer growth both in the lab and in animal models, and it has good safety and drug absorption qualities. It could be used on its own or with other treatments for advanced cancers. There is a clinical trial happening in China to test FCN-159 in patients with melanoma that has NRAS issues.

Reference: Lin S, Zhao X, Zhou Z, Tan H, Chen L, Tan R, Zhang W, Jiang L, Linghu L, Sun J, Zhou J, Li T, Song Y, Wang W. FCN-159: A novel, potent and selective oral inhibitor of MEK1/2 for the treatment of solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1951.