کتابچه خلاصه مقالات همایش


دانلود کتابچه

    KRAS inhibitors: A way for cancer treatment

  • AmirAli Moodi Ghalibaf,1,* Mina AkbariRad,2
    1. Student Research Committee, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
    2. Associate Professor of Internal Medicine, Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


  • Introduction: Today, cancers become one of the major causes of death all over the world. Many processes, either endogenous or exogenous, play critical roles in cancer incidence and progression. By the way, endogenous mutant molecular pathways are known as the key to cancer pathogenesis in many studies. Kirsten rat sarcoma viral oncogene homolog (KRAS) gene is a proto-oncogene which mutations are among the most prevalent tumor drivers. Therefore, the present study is conducted to review the KRAS-G12C activity in cancer pathogenesis and the novel advances in cancer treatment by targetting this proto-oncogene.
  • Methods: A comprehensive search was conducted in electronic databases including Embase, Pubmed, Scopus, and Web of science with the keywords “Cancer”, “KRAS” and all other related MeSH terms up to March 2022. Either original and review studies were reviewed to determine the KRAS-G12C activity, its role, and potential therapeutic agents in this proto-oncogene targetting.
  • Results: KRAS gene belongs to a member of the RAS family and its mutations are genetic drivers of multiple cancer types, including pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer. In a detailed view, KRAS-G12 mutation is a predominant mutation in human cancers, and G12C is the most common mutation subtype in non-small cell lung cancer. In fact, KRAS protein is a signaling GTPase and provides a major signaling axis in tumor cell proliferation and survival which can be known as a key target for cancer treatment. Therefore, inhibiting KRAS, KRAS-G12C, can lead to cancer treatment by trapping the gene and its protein in an inactive GDP-bound state. The last discoveries in terms of finding the reliable KRAS-G12C inhibitor, Sotrasib were proved by FDA in 2021. The studies have been shown that despite KRAS-G12C inhibitor monotherapy can significantly treat some solid tumors, especially non-small cell lung cancer, but applying Sotorasib in combination with agents which target other oncogenic pathways and mediators such as mTOR, insulin-like growth factor 1 receptor, PI3K, ERK, EGFR can improve the therapeutic effects of the treatment regimen. Beyond the KRAS-G12C inhibitor, Sotorasib, resistance, the studies indicate the complexity of the genetic mechanisms of these reactions, which make us uncertain about whether the KRAS-G12C inhibitor resistance can frequently happen or not.
  • Conclusion: In conclusion, it can be stated that despite KRAS-G12C inhibitors, especially Sotorasib, which are known as a revolution in solid tumors treatment, there are some gray areas that need more investigations.
  • Keywords: Cancer, Solid tumors, KRAS, KRAS inhibitors, Sotorasib