Researchers Discover the Weak Points of the Protein That Causes One in 10 Cancers

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Cancer is a disease that affects millions of people worldwide. In at least one in 10 cases, the tumor is driven by mutations in the KRAS gene, discovered in 1982. This gene is so complex that the scientific community has spent four decades trying to find its Achilles heel. Mutations in KRAS are behind almost 90% of pancreatic cancer cases, 40% of colon cancers, and 35% of lung cancers. However, researchers from the Center for Genomic Regulation in Barcelona have finally managed to create a complete map of its weaknesses.

The team has created the first map of the vulnerable sites of the KRAS gene, whose mutations cause millions of tumors. The research was published in the journal Nature, a showcase of the best world science. The KRAS gene is the manual for generating the KRAS protein, a kind of switch that causes the cell to divide. Uncontrolled activation of KRAS causes cells to run amok, multiply, and cause cancer. For decades, it seemed impossible to target this protein with drugs. However, in 2021, the U.S. pharmaceutical company Amgen received FDA approval for sotorasib, an effective drug against lung cancer in people who have a specific mutation in the KRAS gene, which is associated with damage caused by smoking.

The key to the new advance is allosterism, a phenomenon considered “the second secret of life,” by French biologist Jacques Monod, who won the 1965 Nobel Prize in Medicine for discovering it. DNA is the first secret. Monod realized that proteins had some kind of hidden buttons that changed their function. Finding these switches is not easy. The KRAS protein is like the Death Star, the unconquerable space station from the Star Wars film saga. “The protein is quite spherical and has very few sites that you could imagine as binding points for a drug,” says South African bioinformatician André Faure, who works at the Barcelona institution. “It was considered to be impenetrable,” emphasizes his colleague Albert Escobedo.

The authors of the new study explain that the KRAS protein is like the Death Star, the unconquerable space station from the Star Wars film saga. “The protein is quite spherical and has very few sites that you could imagine as binding points for a drug,” says South African bioinformatician André Faure, who works at the Barcelona institution. “It was considered to be impenetrable,” emphasizes his colleague Albert Escobedo.

The new research has created a complete map of the vulnerable sites of the KRAS gene, which will help scientists develop new drugs to target the protein. The research is a significant step forward in the fight against cancer and could lead to new treatments for patients.

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