Study enables development of new anti-cancer drugs
The identification of the structure of a specific protein could represent a significant advance in the development of drugs to treat lung carcinomas represent. Appropriate drugs could fight cancer by promoting its destruction by the cellular machinery.
In a new study involving experts from University of Copenhagen the three-dimensional structure of the protein RAF1 was determined for the first time. This makes it possible to develop special drugs that bind to parts of the protein to degrade RAF1. The study results were published in the journal “Molecular Cell“ published.
Role of oncogenes in the development of cancer
KRAS-Oncogenei.e. genes that cause cancer through a mutation, are for a quarter of all human cancers responsible. This also includes the three tumor types with the highest mortality rate.
The researchers report that these are adenocarcinomas of the lungs, colorectal carcinomas and ductal adenocarcinomas of the pancreas.
Shortage of drugs targeting KRAS oncogenes
According to the research team, the development of drugs against KRAS oncogenes is currently one of the biggest challenges in oncology.
Although KRAS oncogenes were identified four decades ago, the first drug targeting them was approved by the US Food and Drug Administration (FDA) only about a year ago. In the meantime, this drug (sotorasib) has also been approved in the EU.
Sotorasib only effective in specific tumors
True, this was a milestone in the fight against Krebsbut the drug sotorasib is only effective against tumors, which is one of the many Mutations in the KRAS oncogenes according to the team.
This significantly limits the possibilities of effective clinical use of the drug. In addition, there is the problem that people treated with the drug, already within a few months after the treatment develop resistance.
Turning off RAF1 shrinks tumors
In addition to the development of drugs against KRAS oncogenes, one of the currently most active research areas is the identification of inhibitors of the proteins (such as RAF1) that are responsible for the transmission of oncogenic KRAS signals, the researchers explain.
In this context, four years ago, genetically engineered models were developed in mice that faithfully mimic human lung adenocarcinomas. The models showed that switching off the RAF1 protein regression of most tumors causes, reports the team. It is particularly advantageous that this without significant toxic effects successes.
These observations have sparked tremendous interest in finding drugs that can degrade RAF1. According to them, the new study results now open up the possibility for the first time of using such medicinal products degradation of RAF1 to develop.
Improved treatment of lung adenocarcinoma
The researchers explain that these drugs, alone or in combination with KRAS inhibitors, could have an important therapeutic effect in people with lung cancer caused by KRAS oncogenes.
„The information provided by this study opens up a number of options for developing drugs that can degrade RAF1. There is now an opportunity to develop RAF1 degradation drugs‘, summarizes the author of the study Sara García-Alonso in a press release. (as)
Author and source information
This text corresponds to the requirements of medical specialist literature, medical guidelines and current studies and has been checked by medical professionals.
Sources:
- Sara García-Alonso, Pablo Mesa, Laura de la Puente Ovejero, Gonzalo Aizpurua, Carmen G. Lechuga, et al.: Structure of the RAF1-HSP90-CDC37 complex reveals the basis of RAF1 regulation; in: Molecular Cell (veröffentlicht 01.09.2022), Molecular Cell
- Centro Nacional de Investigaciones Oncológicas: The structure of protein RAF1 revealed: a key step in the development of new drugs against lung cancer (veröffentlicht 01.09.2022), CNIO
Important NOTE:
This article contains general advice only and should not be used for self-diagnosis or treatment. He can not substitute a visit at the doctor.