BRAF targets in melanoma. Biological mechanisms, resistance, and drug discovery. Cancer drug discovery and development. Volume 82. Ed. Ryan J. Sullivan. Springer (2015)
As a classic example of a bedside-to-bench-to-bedside paradigm, results from these trials will set the foundation for future clinical and translational studies to elucidate potential synergistic effects of combined BRAF-directed therapy and immunotherapy in patients with BRAF-mutant melanoma. Important questions remain and need to be answered. Will there be synergy between these two strategies? Namely, will the combination increase durable response rates and lead to more complete responses? Will there be increased toxicity with these combinations?
Additional questions regarding timing of therapy and duration of therapy also remain. What is the appropriate sequence and timing, and does therapy need to be continued even in the setting of a complete response or prolonged partial response?
There is some question as to whether or not other not synergy will be seen when immunotherapy is combined with other forms of MAPK pathway blockade (e.g. MEK inhibitors), as MAPK pathway activity is critical to T cell activation and may abrogate T cell responses . These questions all beg answers, which will be provided in the context of translational research and carefully planned clinical trials with appropriate correlative studies.
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