KRAS

An article about the KRAS gene and its significance in medicine

KRAS (Kirsten rat sarcoma viral oncogene homolog) is a gene that encodes a protein called K-Ras, which is a member of the small GTPase superfamily. This protein plays a crucial role in cell signaling pathways that control cell growth, differentiation, and apoptosis. Mutations in the KRAS gene are implicated in the development of various cancers, making it a significant focus of cancer research and targeted therapies.

Structure and Function

The KRAS gene is located on the short arm of chromosome 12 (12p12.1). It encodes a protein that is part of the Ras family of GTPases. These proteins act as molecular switches that cycle between an active GTP-bound state and an inactive GDP-bound state. The active form of K-Ras transmits signals from cell surface receptors to intracellular signaling pathways, such as the MAPK/ERK pathway and the PI3K/AKT pathway, which are involved in cell proliferation and survival.

Role in Cancer

Mutations in the KRAS gene are among the most common oncogenic alterations in human cancers. These mutations often result in a constitutively active K-Ras protein that continuously signals for cell growth and division, bypassing normal regulatory mechanisms. KRAS mutations are particularly prevalent in pancreatic cancer, colorectal cancer, and non-small cell lung cancer.

The most common mutations occur at codons 12, 13, and 61, with the G12D, G12V, and G13D mutations being frequently observed. These mutations impair the GTPase activity of K-Ras, leading to persistent activation of downstream signaling pathways.

Clinical Implications

The presence of KRAS mutations in tumors has significant implications for treatment and prognosis. For instance, in colorectal cancer, KRAS mutations are associated with resistance to EGFR inhibitors such as cetuximab and panitumumab. Therefore, testing for KRAS mutations is a critical step in the management of patients with certain types of cancer.

Recent advances in targeted therapy have led to the development of KRAS inhibitors, such as sotorasib, which specifically target the G12C mutation. These therapies represent a promising approach for treating cancers driven by KRAS mutations.

Research and Future Directions

Ongoing research aims to better understand the biology of KRAS and to develop more effective therapies for KRAS-mutant cancers. Strategies include the development of direct KRAS inhibitors, targeting downstream effectors, and exploring combination therapies to overcome resistance mechanisms.

Also see

• Ras subfamily
• MAPK/ERK pathway
• PI3K/AKT pathway
• Oncogene
• Tumor suppressor gene