Purpose of review: The unique structure made Kirsten rat sarcoma (KRAS) 'undruggable' for quite an extended period. The functional mechanism of this small protein is well illustrated. However, there is no precision medicine for nonsmall cell lung cancer (NSCLC) patients burden with KRAS mutation. The attempts made by scientists to make challenge history against KRAS mutation and their druggable targets are worth elucidating.
Recent findings: The appearance of orphan drug AMG510 in the market specifically targeting KRASG12C is a tremendous breakthrough. Several KRAS inhibitors are under development now. More studies focus on combo treatment of KRAS inhibition and immune checkpoint inhibitors (ICIs). Recent preclinical and clinical investigations have been reported that NSCLC patients with KRAS mutation can benefit from ICIs.
Summary: The current review elucidates the development of KRAS inhibitors from basic research to clinical precision medicines. We retrospectively analyze the development of KRAS mutation targeting drugs and discuss the investigations for future development of KRAS inhibitors.
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