BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: Checkpoint kinase 1 (Chk1; CHEK1); MAP kinase-activated protein kinase 2 (MAPKAPK2; MK2); K-Ras (KRAS); BRAF

July 16, 2015 7:00 AM UTC

Studies in patient samples and mice suggest combining inhibitors of Chk1 and MAPKAPK2 could help treat KRAS- or BRAF-mutant tumors. In tumor samples from patients with lung or colon adenocarcinomas, levels of Chk1 and MAPKAPK2 were higher in samples harboring KRAS mutations than in samples with wild-type KRAS. In five pancreatic tumor samples with mutant KRAS and a lung tumor sample with mutant BRAF, small molecule inhibition of Chk1 and MAPKAPK2 increased apoptosis compared with either agent alone. In mice bearing KRAS- or BRAF-mutant xenograft lung or colorectal tumors, the Chk1 and MAPKAPK2 inhibitors decreased tumor growth compared with either agent alone, whereas the combination had no effect on the growth of tumors expressing wild-type KRAS or BRAF. Next steps could include testing combined inhibition of Chk1 and MAPKAPK2 in a clinical trial.

Eli Lilly and Co. has the Chk1 inhibitor LY2606368 in Phase II testing to treat head and neck cancer...