Targeting KRAS(G12C): From inhibitory mechanism to modulation of antitumor effects in patients Editorial
| Authors: | Kim, D.; Xue, J. Y.; Lito, P. |
| Title: | Targeting KRAS(G12C): From inhibitory mechanism to modulation of antitumor effects in patients |
| Abstract: | KRAS mutations are among the most common genetic alterations in lung, colorectal, and pancreatic cancers. Direct inhibition of KRAS oncoproteins has been a long-standing pursuit in precision oncology, one established shortly after the discovery of RAS mutations in human cancer cells nearly 40 years ago. Recent advances in medicinal chemistry have established inhibitors targeting KRAS(G12C), a mutation found in ∼13% of lung adenocarcinomas and, at a lower frequency, in other cancers. Preclinical studies describing their discovery and mechanism of action, coupled with emerging clinical data from patients treated with these drugs, have sparked a renewed enthusiasm in the study of KRAS and its therapeutic potential. Here, we discuss how these advances are reshaping the fundamental aspects of KRAS oncoprotein biology and the strides being made toward improving patient outcomes in the clinic. © 2020 Elsevier Inc. Kim et al. review recent advances in the effort to therapeutically target KRAS(G12C), one of the most common oncoproteins in lung cancer and one previously thought to be undruggable. Mechanistic insights with implications for the emergence of resistance and optimal combination therapy are discussed. © 2020 Elsevier Inc. |
| Journal Title: | Cell |
| Volume: | 183 |
| Issue: | 4 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2020-11-12 |
| Start Page: | 850 |
| End Page: | 859 |
| Language: | English |
| DOI: | 10.1016/j.cell.2020.09.044 |
| PUBMED: | 33065029 |
| PROVIDER: | scopus |
| PMCID: | PMC7669705 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 1 December 2020 -- Source: Scopus |
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