RAS (KRAS, NRAS and HRAS) is the most common mutation gene family in tumors. Ras gene is also the first identified human oncogene, which can be divided into KRAS, NRAS and HRAS. It was discovered by Robert Weinberg in 1982.
As the most common oncogene in human tumors, ras protein encoded by ras gene mutation prevents GTP from transforming into GDP, resulting in constitutive activation of Raf kinase in cells. When RAS is activated, it can activate several downstream signaling pathways, including MAPK signaling pathway, PI3K signaling pathway, and ral GEFs signaling pathway. These signaling pathways play an important role in promoting cell survival, proliferation and cytokine release.
The most common RAS mutations were pancreatic cancer (97.7%), colorectal cancer (52.2%), myeloma (42.6%), lung adenocarcinoma (30.9%), and so on. However, such an important and widespread ras gene mutation, after more than 30 years of research, there is still no effective drug targeting RAS. Because it is difficult to develop Ras inhibitors, RAS has also been labeled as a non patent drug.
Chen Gen: new technology conquers the most difficult cancer gene, from difficulty to new hope
Recently, a research team at the University of Leeds discovered the weakness of the mutant protein, which brought hope for the development of new and powerful drugs. Among them, the researchers of Leeds University make full use of the patent affine biotechnology platform of the school of molecular and cell biology, and give full play to its advantages to accurately locate the available drug "pocket" on the protein, so as to carry out effective treatment.
The researchers believe that this fact enables them to prove that affine technology can have such a huge impact and bring huge benefits when it comes to treating challenging pathology. We have found small molecules that bind to Ras, so in the next few years, it will be an exciting process to explore these small molecules and develop effective drugs.
It is worth mentioning that at present, many frontier therapies aiming at Ras target drugs in different directions are in the early stage of preclinical and clinical trials. For example, Amgen announced the top-level data of the phase I clinical trial of its KRAS inhibitor amg510 at the 2009 ASCO annual meeting. In addition, amjin announced the latest R & D Progress of amg510 on wclc2019. The data show that amg510 has good efficacy, safety and tolerance in targeting NSCLC patients with KRAS G12C mutation.
It can be predicted that the continuous breakthroughs in the research of new methods to deal with RAS will not only accelerate the research and development of new drugs, but also help drug developers screen the matched subjects in clinical trials, provide patients with the safety and effectiveness of specific therapeutic drugs, help screen patients who may benefit, improve the therapeutic effect and reduce medical costs.
