The importance of translating knowledge from basic to the clinic is once again evident in the new publication inCancer Cell by one of our MOM professors, Dr. Barbacid.
In 2018, Dr. Barbacid’s group already published in Cancer Cell a very important article for lung cancer, in which they identified the elimination of RAF1 as a new therapeutic target for the 20% of tumors mediated by KRAS. However, since then, this approach had become a real nightmare for researchers and clinicians, since it appears that the inhibitors being tested did not work and it was not known why.
We finally have the answer, Barbacid´s group has continued to investigate the molecular mechanisms of RAF1 and have managed to demonstrate, using a genetically modified mouse model, that the kinase activity of RAF1 is not necessary for KRAS-oncogenic signaling. It is its anti-apoptotic activity, which is essential for the tumor to survive.
This discovery has been somehow completely unexpected for everyone. It explains why all the clinical approaches using inhibitors against RAF1 did not give the expected results. Based on the results obtained by this group, the strategy should be to directly degrade the protein using what they call “degrons”, small chemical molecules capable of degrading specific proteins.
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