PARIS: Scientists have made significant strides toward developing new treatments for some of the most lethal types of cancer by identifying ways to target the ‘Death Star’ protein, also known as KRAS.
Responsible for one in 10 cancer cases, KRAS mutations drive 40% of lung cancers, 45% of bowel cancers, and a staggering 90% of pancreatic cancers. The protein likened to a ‘Death Star’ due to its drug-resistant and impenetrable surface, has posed challenges in treatment.
Researchers from the Wellcome Sanger Institute, in collaboration with the Centre for Genomic Regulation in Spain, utilized a groundbreaking technique called deep mutational scanning to comprehensively map the protein. Their discovery identified four distinct ‘pockets’ on the protein’s surface, known as allosteric sites, which could serve as promising targets for future drugs.
These sites, crucial for triggering changes in the protein’s shape and function, offer potential vulnerabilities that may pave the way for new treatments, controlling the protein and inhibiting its role in cancer progression.
Dr. André Faure, co-author of the study, explained the significance, stating, “For the purposes of drug discovery, it’s like turning the light on and laying bare the many ways we can control a protein.” The analysis, published in the journal Nature, also highlighted that small alterations to the Death Star protein could dramatically alter its behavior. This revelation opens the door to new strategies that can regulate the protein’s unwanted actions without impacting its normal function in non-cancerous tissues.
Despite decades of research and numerous scientific publications, only two drugs have been approved for clinical use to target KRAS. The researchers are optimistic that their findings could lead to the development of safer, more effective treatments with fewer side effects.
Senior author Dr. Ben Lehner emphasized the significance of the study, stating, “The big challenge in medicine isn’t knowing which proteins are causing diseases but not knowing how to control them. Our study represents a new strategy to target these proteins and speed up the development of drugs to control their activity.”