Abstract
Around 8–12% of patients with advanced colon rectal cancer (CRC) present with BRAF alterations, in particular V600E mutation, which is associated with right-side, poorly differentiated and mucinous type tumors. The presence of BRAF mutation (BRAF-mt) has been identified as a hallmark of poor prognosis and treatment optimization in this patient subgroup is an important goal. Currently, the standard of care is an aggressive strategy involving triplet chemotherapy and anti-VEGF agents, but new therapeutic approaches are emerging. Very promising results have been obtained with targeted therapy combinations, such as anti-BRAF agents plus anti-EGFR agents. Furthermore, around 60% of BRAF-mt patients show a strong association with high microsatellite instability (MSI-H) and immune checkpoint inhibitors could represent the new standard of care for this subgroup. The focus of this review is to summarize current strategies for BRAF-mt CRC treatment and highlight new therapeutic options.
Highlights
Colorectal cancer (CRC) is a molecularly heterogeneous disease the second most frequent cause of cancer-related death worldwide [1, 2]
BRAF mutations in advanced disease are observed in 8–12% of patients, and T1799A transversion in exon 15, which results in a valine amino acid substitution (V600E), is the most frequent alteration
There is a strong association between BRAF V600E mutation and microsatellite instability and immunotherapy could represent a new standard of care in this subgroup [6, 7]
Summary
Colorectal cancer (CRC) is a molecularly heterogeneous disease the second most frequent cause of cancer-related death worldwide [1, 2]. BRAF mutations in advanced disease are observed in 8–12% of patients, and T1799A transversion in exon 15, which results in a valine amino acid substitution (V600E), is the most frequent alteration. BRAF is considered a negative prognostic biomarker and patients harboring this mutation have limited response to chemotherapy. The best treatment option appears to be triplet chemotherapy plus anti-VEGF agents, but data are still limited [5]. There is a strong association between BRAF V600E mutation and microsatellite instability and immunotherapy could represent a new standard of care in this subgroup [6, 7]. The present summarizes the current therapeutic options for BRAF-mt CRC
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