The Oncogenic KRAS in Solid Cancer: Functional Signaling

The Kirsten rat sarcoma viral oncogene homolog, or KRAS gene, is an oncogene that produces the small GTPase transductor protein known as KRAS. Because it may transmit outside signals to the cell nucleus, KRAS plays a role in controlling cell division. The inability of the KRAS protein to transition between active and inactive states is caused by activating mutations in the KRAS gene, which results in cell transformation. This study summarizes what is now known about the mechanism governing KRAS gene regulation and highlights some of the characteristics of the KRAS gene and KRAS protein. Targeted therapies have significantly revolutionized the treatment and outcome of cancer, which is currently the top cause of mortality worldwide. KRAS is the most frequently mutated oncogene and has garnered significant interest. Many investigations on the role of KRAS in the development and progression of cancer disorders are contributing to the ongoing updating of our understanding of KRAS. Nevertheless, following decades of drug-targeting studies, KRAS has been determined to be a difficult therapeutic target – even “undruggable.” Unexpected progress has been made recently in the development of KRAS-specific medications, particularly in the area of KRAS (G12C) inhibitors, including sotorasib (AMG510) and adagrasib (MRTX849), which have shown promising outcomes in clinical studies. It is exciting to note that AMG510 was the first KRAS (G12C) therapeutic target to be authorized for clinical use. Overall, we can say, KRAS is a gene encoding a GTPase that regulates cell signaling pathways controlling growth and survival. Mutations, especially at codons G12, G13, and Q61, result in a constantly active KRAS protein, driving uncontrolled cell division. These mutations are common in cancers such as pancreatic, colorectal, and nonsmall cell lung cancer. Mutant KRAS activates pathways such as MAPK and phosphoinositide 3-kinase, promoting tumor growth, resistance to therapy, and poor prognosis, making it a critical target in cancer treatment. The most recent knowledge about the basic properties of KRAS, the connection between KRAS mutations and tumor immune evasion, and the developments in KRAS targeting, specifically KRAS (G12C), is compiled in this review.