Journal
CANCER DISCOVERY
Volume 11, Issue 6, Pages 1345-1352Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-20-1616
Keywords
-
Categories
Funding
- NIH Cancer Center Support Grant [CA016672]
Ask authors/readers for more resources
KRAS mutations drive cancer growth, but the development of resistance to targeted therapies remains a challenge. Understanding the mechanisms of resistance and developing combination strategies are crucial for long-term disease control.
KRAS mutations are among the most common drivers of human carcinogenesis, and are associated with poor prognosis and an aggressive disease course. With the advent of KRAS(G12C) inhibitors, the RAS protein is now targetable, with such inhibitors showing marked clinical responses across multiple tumor types. However, these responses are short-lived due to the development of resistance. Preclinical studies now suggest MAPK reactivation, stimulation of CDK4/6dependent cell-cycle transition, and immune defects as possible mechanisms of resistance. Devising strategies to overcome such resistance mechanisms, which are a barrier to long-term clinical response, remain an active area of research. Significance: Although KRAS-targeted cancer therapy is revolutionary, tumors rapidly develop resistance. Understanding the mechanisms driving this resistance and designing combination strategies to overcome it are integral to achieving long-term disease control.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available