The next steps in next-gen sequencing of cancer genomes
D. Neil Hayes, William Y. Kim
D. Neil Hayes, William Y. Kim
Published February 2, 2015
Citation Information: J Clin Invest. 2015;125(2):462-468. https://doi.org/10.1172/JCI68339.
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The next steps in next-gen sequencing of cancer genomes

Abstract

The necessary infrastructure to carry out genomics-driven oncology is now widely available and has resulted in the exponential increase in characterized cancer genomes. While a subset of genomic alterations is clinically actionable, the majority of somatic events remain classified as variants of unknown significance and will require functional characterization. A careful cataloging of the genomic alterations and their response to therapeutic intervention should allow the compilation of an “actionability atlas” and the creation of a genomic taxonomy stratified by tumor type and oncogenic pathway activation. The next phase of genomic medicine will therefore require talented bioinformaticians, genomic navigators, and multidisciplinary approaches to decode complex cancer genomes and guide potential therapy. Equally important will be the ethical and interpretable return of results to practicing oncologists. Finally, the integration of genomics into clinical trials is likely to speed the development of predictive biomarkers of response to targeted therapy as well as define pathways to acquired resistance.

Authors

D. Neil Hayes, William Y. Kim

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Figure 2

Integration of pathway and organ site clinical trials.

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Integration of pathway and organ site clinical trials. (A) Current oncol...
(A) Current oncology clinical trials are generally structured based on organ site, in which novel compounds (A, B, and C) are tested in specific cancers. (B) There are, however, commonalities in oncogenic pathways among cancers such as activation of the EGFR, FGFR3, and BRAF pathways. These pathways can be targeted with relatively specific inhibitors (X, Y, and Z). Some clinical trials are beginning to enroll patients on the basis of pathway activation (i.e., FGFR or BRAF mutations). (C) This approach, while reasonable, will likely require attention to both pathway activation and organ site. For example, BRAF mutations are found in a number of cancers including melanoma, thyroid, colon, and bladder. While BRAF inhibition has shown efficacy in BRAF-mutant melanoma and thyroid cancer, it does not appear to benefit patients with BRAF-mutant CRC. Whether BRAF inhibition in bladder cancer is of use remains unknown.