A step towards more drugs for lung cancer, by unveiling a protein

Madrid, Sep 1 (EFE) .- A target for developing new drugs against lung cancer is the RAF1 protein, but first its structure had to be known and that is what a team of Spanish and Danish researchers has revealed, according to Molecular Cell.

The groups of Mariano Barbacid, at the National Cancer Research Center in Spain (CNIO), and Guillermo Montoya, of the University of Copenhagen, have managed to determine the structure of the RAF1 protein, a therapeutic target against tumors associated with KRAS oncogenes .

This oncogene was one of the first to be discovered, it is the one that is most frequently mutated in humans and is involved in a quarter of tumors in general, including the three with the highest mortality: lung adenocarcinoma, colorectal carcinoma and cancer. ductal adenocarcinoma of the pancreas.

One of the most active areas of research against this oncogene is to identify protein inhibitors, such as RAF1, which are responsible for transmitting KRAS oncogenic signals.

The research now published has made it possible to identify structural vulnerabilities in RAF1, which makes it possible to design drugs capable of destroying it.

Barbacid’s lab had previously shown, in genetically modified mouse models, that deletion of the RAF1 protein induced regression of most tumors without causing significant toxicities.

Determining the three-dimensional structure of RAF1 “is a key step”, because it reveals the parts of the protein to which a drug could be chemically attached, and promote its destruction by the cellular machinery.

“The information provided by this study opens up a range of options for developing drugs that manage to degrade RAF1”, highlighted Sara García Alonso, from the CNIO and one of the main researchers of the study.

In this way, he considered, “a window of opportunity is now opening to design RAF1 degraders with an important therapeutic effect in patients with lung adenocarcinoma induced by KRAS oncogenes.”

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