Conclusion

BRAF targets in melanoma. Biological mechanisms, resistance, and drug discovery. Cancer drug discovery and development. Volume 82. Ed. Ryan J. Sullivan. Springer (2015)


Treatment options for advanced stage cancers, especially metastatic melanoma, have advanced with the advent of effective targeted therapy, necessitating the use of molecular diagnostics for clinical decision making. Standard mutation detection techniques may still remain the optimal choice in somatic testing, in particular when evaluating an individual mutation or gene (e.g. BRAF or KIT), as these tests have been validated and are cost effective with relative quick turnaround time. The information garnered with next generation sequencing provides clinicians with a large amount of information, extending past the presence or absence of a particular mutation (e.g. V600E in BRAF). However, many of the mutations identified beyond those available with targeted mutation screening may not be clinically actionable. As MPS strategies are used to profile tumors, they have become available in Clinical Laboratory Improvement Amendments (CLIA) certified laboratories, so the data generated will be usable in the clinical setting. As concurrent mutations are evaluated and detected, it is possible to ascertain the presence of mutations which would predict for resistance to a specific targeted therapy (e.g. additional pathway mutations, such as in MAP2K1). Thus, MPS provides valuable information with potential implications regarding treatment options for patients at the time of initial evaluation. More importantly, the use of MPS at the time of disease relapse, progression, or development of resistance to therapy to classify the genetic landscape within an individual’s tumor will provide information regarding potential therapeutic options. From a research perspective, the identification of somatic mutations and mechanisms of resistance will further guide research endeavors and clinical trial development as clinicians seek out improved therapeutic options.

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