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Han, ZhaoYong; Zhou, Ding; Wang, JiaMan; Jiang, Bruce; Liu, XiYu
Biochimica et biophysica acta. Reviews on cancer, January 2022, 20220101, Volume: 1877, Issue: 1Journal Article
KRAS is the most commonly mutated oncogene in human tumors, especially in lung, pancreatic, and colorectal cancers. Small-molecule inhibitors targeting mutant KRASG12C demonstrated promising anti-tumor effect in patients with non-small cell lung cancer harboring KRASG12C mutation, while the intrinsic and acquired drug resistance occurred frequently and might be inevitable. Unlike the protein-level inhibition approach, gene silencing/editing tools for DNA-level knockout and RNA-level knockdown of mutant KRAS may be advantageous since these approaches directly eliminate the production of mutant KRAS-encoded protein. An in-depth understanding of KRAS biology, drug resistance to KRASG12C inhibitors and gene silencing/editing methods applied for anti-KRAS therapy may give new insight into the therapeutic strategy for cancer treatment.
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