What about cancer resistance to KRAS inhibitors? This study finds a solution.

After screening 16,019 genes through shRNA screening, researchers at the Francis Crick Institute and the British Cancer Institute (ICR) found that the research of KRAS-G12C inhibitor ARS-1620, and the study of insulin growth factor-1 receptor (IGF1R) inhibitor linsib, combined with mTOR inhibitors, were significantly reduced in size and longer-lasting effectThe results were recently published in the journal Science Translational MedicineRAS family protein is divided into three main categories: KRAS, HRAS, NRAS, of which the proportion of KRAS gene mutation symon stakes of more than 80%, it is one of the most common cancer-causing genesRAS protein regulation includes several downstream pathways, including the MAPK Signaling Pathway (RAS-RAF-MEK-ERK), and PI3K/AKT/mTOR, which control several key cellular activities, including proliferation, differentiation, survival, and angiogenesisTHE KRAS mutation occurs in more than 90% of pancreatic cancers, 40% of colorectal cancers, and 16% of lung adenocarcinoma casesIGF1R is a membrane protein receptor with tyrosine kinase activity that is often overexpressed in lung cancerIt is a key factor in malignant transformation in the upstream of MARK and PI3K signaling pathways, and it is also one of the main causes of resistance to eGFR inhibitorsmembrane receptor protein IGF-1R regulates the mapK and PI3K/AKT/mTOR signaling pathways downstream (Photo: Source: Supplied)researchers found that knocking out the MTOR gene makes cells significantly sensitive to KRAS and IGF1R inhibitorsWhen three signaling pathways IGF1R, MAPK and PI3K/AKT/mTOR were blocked at the same time, cancer cells carrying THE KRAS mutation could not surviveUsing the KRAS-G12C inhibitor ARS-1620 alone causes tumor cells to develop resistance and grow back in a few weeksIn the study of KRAS-G12C inhibitor ARS-1620, IGF1R inhibitor linsitinib, combined with mTOR inhibitors, the three-combination therapy, can significantly reduce the size of mouse and human tumors, and the efficacy is significantly more durableThis combination therapy has the potential to prevent or delay the resistance of KRAS-G12C inhibitorsin the study of KRAS-G12C inhibitor ARS-1620, and in the study of IGF1R inhibitor linsitinib, a combination of combination therapies with mTOR inhibitors, have significant efficacy in lung cancer with KRAS-G12C mutations (Photo Source: Source: Resources 1)one of the authors of this paper, DrJulian Din, believes that the current study provides a new method to improve the efficacy of the target-to-target KRAS proteinKRAS mutations tend to be more invasive "This provides a clear direction on how to better use KRAS-G12C inhibitors in clinical practice, and how to avoid possible cancer resistance evolution when used as a single drug." " References: Romero-Clavijo et al (2019) Development of the combination therapies to maximize the impact of KRAS-G12C in lung cancer Science Translational Medicine https://doi.org/10.1126/scitranslmed.aaw7999 Researchers Develop New Class of Lung Cancer Drugs Retrieved Sep 19, 2019, from https:// Can a combo treatment boost KRASs in lung cancer? Retrieved Sep 19, 2019, from https:// Two Is Better Than One: Combining IGF1R and MEK Blockade as a Novel Development Field Strategy Strategy Against Kras-Mumin Lung Cancer Retrieved Sep 19, 2019, from https://cancerdiscovery.aacrjournals.org/content/3/5/491.figures-only