[Cell Sub-Journal] The structure of protein RAF1 revealed: a key step in the development of new anti-lung cancer drugs

This article is original from Translational Medicine Network, please indicate the source for reprinting 

Author: Sophia

Introduction: One of the major challenges in oncology is the development of drugs that target the KRAS oncogene

Although Mariano Barbacid's research group had discovered the KRAS oncogene as early as 40 years ago, the first drug to fight them - Sotorasib, Amgen , which was approved by the FDA only a year ago

The results of a new study, published Sept.

overview

 01 

In addition to developing drugs against KRAS, one of the most active studies in this field is currently seeking to identify inhibitors of proteins, such as RAF1, the protein responsible for transmitting KRAS oncogenic signaling

In 2020, the CNIO team used a mouse model that accurately reproduces the human disease to induce aggressive lung tumors by activating the KRAS oncogene and deactivating the p53 tumor suppressor, which is responsible for a high percentage of human lung glands.

These findings shed light on the development of new therapies for KRAS-mutant tumors and demonstrate the importance of developing inhibitors that specifically target RAF1

RAF kinase

 02 

RAF kinases are RAS-activated enzymes that initiate signaling through the MAPK cascade to control cell proliferation, differentiation, and survival

RAF1 downgrade 

 03 

Mariano Barbacid's lab used a transgenic mouse model that faithfully reproduced human lung adenocarcinoma

Determining the three-dimensional structure of RAF1 is a critical step in achieving this goal, as it uncovers the moiety in the protein where the drug can chemically anchor and facilitate its destruction by cellular machinery (cells with cleaning mechanisms that degrade defective or useless proteins)

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

References:

This article is intended to introduce the progress of medical research and cannot be used as a reference for treatment plans

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