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The promising role of TGF-βRII mutations and EGFR immunostaining in response to anti-EGFR therapies
In sporadic colorectal cancer, the presence of mutations in the RAS genes means a lack of response to anti-EGFR drugs, while the absence of mutations in these genes does not guarantee a good response in terms of survival or relapse. In addition, the presence of genetic abnormalities in the TGF-β pathway is responsible for increased activation of the MAPK pathway and could have an impact on the response to anti-EGFR.
Our study enrolled 43 advanced CRC cases, on which we performed immunohistochemical analysis of EGFR protein using monoclonal anti-EGFR antibody (Clone IHC565) and a molecular analysis of the exon 3 of TGFBR2 gene was realized.
The obtained results of this retrospective study highlight the impact of somatic genetic abnormalities of the TGFBR2 gene on the functioning of the RAS/RAF/MAPK signaling pathway and on the eventual response to Cetuximab for mCRC patients.Six variants were found in patients with advanced tumor stage, especially in patients with wild-type RAS (13.8%) and in those with high EGFR expression (31.2%). Overall survival for patients with TGFβRII mutation was below average in 66.7% and response to cetuximab ranged from 2 to 6 months in wild-type RAS patients. These results highlight the importance of integrating the research of TGFBR2 gene mutations as well as EGFR immunohistochemical expression data, in the list of parameters leading to the selection of mCRC patients for anti-EGFR therapy.
The approach we propose through these research results has the potential to adapt current targeted therapies (anti-EGFR) to the biological characteristics of sporadic CRC through TGFβ pathway and could thus decrease the risk of administering expensive and potentially toxic treatments to patients unnecessarily.
The authors.
Has not received any funding.
All authors have declared no conflicts of interest.
