DGH - Capítulos (ou partes) de livros
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Browsing DGH - Capítulos (ou partes) de livros by Subject "BRAF"
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- Targeting Colon Cancers with Mutated BRAF and Microsatellite InstabilityPublication . Matos, Paulo; Jordan, PeterThe subgroup of colon cancer (CRC) characterized by mutation in the BRAF gene and high mutation rate in the genomic DNA sequence, known as the microsatellite instability (MSI) phenotype, accounts for roughly 10% of the patients and derives from polyps with a serrated morphology. In this review, both features are discussed with regard to therapeutic opportunities. The most prevalent cancer-associated BRAF mutation is BRAF V600E that causes constitutive activation of the pro-proliferative MAPK pathway. Unfortunately, the available BRAF-specific inhibitors had little clinical benefit for metastatic CRC patients due to adaptive MAPK reactivation. Recent contributions for the development of new combination therapy approaches to pathway inhibition will be highlighted. In addition, we review the promising role of the recently developed immune checkpoint therapy for the treatment of this CRC subtype. The MSI phenotype of this subgroup results from an inactivated DNA mismatch repair system and leads to frameshift mutations with translation of new amino acid stretches and the generation of neo-antigens. This most likely explains the observed high degree of infiltration by tumour-associated lymphocytes. As cytotoxic lymphocytes are already part of the tumour environment, their activation by immune checkpoint therapy approaches is highly promising.
- Therapeutic approaches targeting the serrated pathway of colorectal cancer characterized by mutation in the BRAF gene and overexpression of GTPase RAC1bPublication . Matos, Paulo; Gonçalves, Vânia; Jordan, PeterAround 30% of all colorectal cancer cases are derived from the serrated polyp pathway and mostly carry a mutation in the BRAF gene. Here, we review the current knowledge about the association of this tumor subtype with the CpG island methylator and microsatellite instability phenotypes, immune cell infiltration, and overexpression of GTPase Rac1b. The corresponding therapeutic approaches for targeting these molecular characteristics are presented and critically discussed.