Cancer: A treatment for KRAS-mutant cancer

A new anti-cancer drug that targets a common and specific genetic abnormality has shown promise in a study of mouse and human tumours. The research, which includes the first known report of KRAS inhibitor treatment in human clinical trials, is revealed in this week’s Nature.

Many human cancers are triggered by a mutation in the KRAS oncogene. Around 13% of lung adenocarcinomas, 3% of colorectal cancers and 2% of other solid tumours contain a mutation in KRAS. Here, Jude Canon and colleagues report the development of an anti-cancer drug called AMG 510, that works by inhibiting the activity of this oncogene.

In mouse models of Kras-mutant cancer, the treatment helped to shrink, and in some cases eradicate, the growing tumour. The study also reports positive responses in two patients with KRAS-mutant tumours from a dose-escalation study. After 6 weeks of treatment, the tumour of one patient had shrunk by 34% and the tumour of the other patient had shrunk by 67%. This is the first report of patients with cancer who responded to a direct, mutant-selective KRAS inhibitor.

Furthermore, in mouse models of colorectal cancer, the treatment also created a pro-inflammatory microenvironment around the tumour. This effect made the tumour more sensitive to other cancer drugs, generated an adaptive immune response and lead to durable cures for the animals. Taken together, the results suggest that the drug could work well alone or in combination with other anti-cancer strategies.