Targeting KRAS in Cancer: Promising Therapeutic Strategies

SIMPLE SUMMARY: Since the Kirsten rat sarcoma viral oncogene homolog (KRAS) is mutated in about 25% of all human cancers and is at the center of pathways involved in tumorigenesis, it is necessary to compile and highlight the novel therapeutic strategies behind targeting this oncoprotein in cancer. Over the years, many have studied various methods to directly target KRAS with no success. Fortunately, there has been more success in targeting other proteins along the RAS pathway to yield a therapeutic response. However, some recent findings show promising results indicating that we are one step closer to developing an effective inhibitor that directly targets KRAS. The review presented here summarizes these recent findings and emphasizes the need to continue the search for the most optimal KRAS inhibitor that can be used to treat and potentially even cure certain tumor types. ABSTRACT: The Kirsten rat sarcoma viral oncogene homolog (KRAS) is mutated in approximately 25% of all human cancers and is known to be a major player promoting and maintaining tumorigenesis through the RAS/MAPK pathway. Over the years, a large number of studies have identified strategies at different regulatory levels to tackle this ‘difficult-to-target’ oncoprotein. Yet, the most ideal strategy to overcome KRAS and its downstream effects has yet to be uncovered. This review summarizes the role of KRAS activating mutations in multiple cancer types as well as the key findings for potential strategies inhibiting its oncogenic behavior. A comprehensive analysis of the different pathways and mechanisms associated with KRAS activity in tumors will ultimately pave the way for promising future work that will identify optimum therapeutic strategies.