Structure of the RAF1 protein: a critical step in the development of new anti-lung cancer drugs

While the KRAS oncogene was discovered 40 years ago by Mariano Barbacid's group, the first drug to fight the KRAS oncogene -- Amgen's sotorasib -- was approved by the FDA only a year ago

RAF1 and lung adenocarcinoma

In addition to the development of anti-KRAS drugs, one of the most active research areas currently is the search for inhibitors of proteins responsible for transmitting KRAS oncogenic signals, such as RAF1

In this regard, Mariano Barbacid's laboratory, using a transgenic mouse model that realistically reproduced human lung adenocarcinoma, demonstrated four years ago that elimination of the RAF1 protein resulted in regression of most tumors without significant toxic effects

Goal: Reduce RAF1

These observations have sparked great interest in finding drugs that can degrade RAF1

Determination of the three-dimensional structure of RAF1 is a critical step toward this goal, as it reveals the portion of the protein to which the drug can chemically anchor and facilitate its destruction by cellular mechanisms (cells with degraded defective or useless protein cleaning mechanisms)

The principal investigators responsible for this work are Sara García-Alonso from CNIO and Pablo Mesa from the Molecular and Structural Biology Group at the University of Copenhagen

"The information provided by this study provides a range of options for developing drugs that can degrade RAF1," said García-Alonso

Journal Reference:

1. Sara García-Alonso, Pablo Mesa, Laura de la Puente Ovejero, Gonzalo Aizpurua, Carmen G.