Title:Targeting K-Ras Mutations Show Promise Towards Ending Ras’s
“Undruggable” Era
Volume: 29
Issue: 12
Author(s): Paul D. Adams*Djamali Muhoza
Affiliation:
- Department of Chemistry and Biochemistry, University of Arkansas at Fayetteville, 72701, Arkansas, AR 72701, USA
Keywords:
Ras proteins, K-Ras mutations, undruggable, combination therapy, G12C, K-Ras inhibitors.
Abstract: It has almost been 40 years since the Ras proteins were discovered as the first human
oncogenes. They remain among the most important genes for regulating mammalian cell growth and
are involved in more than a quarter of human cancers. Out of 167 members of the Ras superfamily, KRas
mutations are the most abundant in human cancers. Particularly, the K-Ras G12C mutations are
known to be involved in pancreatic, colon and lung cancers as well as leukemias. Though progress has
been made, approaches targeting Ras proteins for therapeutic purposes remain challenging. No drugs
treating Ras-related cancers are currently on the market. However, there is now renewed interest in the
Ras area, and newer approaches have highlighted the targeting of several types of tumors and treating
cancer patients. This review will summarize recent K-Ras drug candidates and approaches in the preclinical,
clinical and post-clinical pipelines that show promise for targeting and reducing Ras-related
tumors. Macromolecules such as mRNA vaccines, siRNA, and T-cell receptors that target Ras will also
be discussed. The newer molecules and the recent approaches to be discussed suggest that the
“undruggable” era of Ras proteins could be coming to an end.
