BRAF targets in melanoma. Biological mechanisms, resistance, and drug discovery. Cancer drug discovery and development. Volume 82. Ed. Ryan J. Sullivan. Springer (2015)
The combination of BRAF and MEK inhibitors appears to represent a step forward in therapy for BRAFV600 mutant melanoma, leading to improved outcomes via enhanced blockade of the MAPK pathway. However, acquired resistance and disease progression still occurs in less than one year for most patients, suggesting that blockade of additional signaling pathways and alternate treatment strategies may be necessary to achieve more durable clinical benefit. Clinicians should note that the toxicity profile is distinct from BRAF inhibitor monotherapy, with decreased incidence of cSCCs and less theoretical concern of promotion of other RAS mutated malignancies . However, systemic side effects including pyrexia, hypotension, and neutropenia occur more frequently with this regimen and patients should be monitored closely.
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