Abstract: The diagnosis, classification, and management of cancer are traditionally dictated by the site of tumor origin, for example, breast or lung, and by specific histologic subtypes of site-of-origin cancers (e.g., non-small cell versus small cell lung cancer). However, with the advent of sequencing technologies allowing for rapid, low cost, and accurate sequencing of clinical samples, new observations suggest an expanded or different approach to the diagnosis and treatment of cancer-one driven by the unique molecular features of the tumor. We discuss a genomically driven strategy for cancer treatment using BRAFas an example. Several key points are highlighted: (i) molecular aberrations can be shared across cancers; (ii) approximately 15% of all cancers harbor BRAF mutations; and (iii) BRAF inhibitors, while approved only for melanoma, have reported activity across numerous cancers and related disease types bearing BRAF aberrations. However,BRAF-mutated colorectal cancer has shown poor response rate to BRAF inhibitor monotherapy, striking a cautionary note. Yet, even in this case, emerging data suggestBRAF-mutated colorectal cancers can respond well to BRAF inhibitors, albeit when administered in combination with other agents that impact resistance pathways. Taken together, these data suggest that molecular aberrations may be the basis for a new nosology for cancer.Mol Cancer Ther; 15(4); 1-15. ©2016 AACR.
Michelle L. Turski, Smruti J. Vidwans, Filip Janku, Ignacio Garrido-Laguna, Javier Munoz, Richard Schwab, Vivek Subbiah, Jordi Rodon, and Razelle Kurzrock.
1 CollabRx Inc., San Francisco, California.
2 Department of Investigational Cancer Therapeutics – a Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
3 Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
4 Banner MD Anderson Cancer Center, Gilbert, Arizona.
5 Center for Personalized Cancer Therapy, Moores Cancer Center, University of California, San Diego, California.
6 Vall d’Hebron Institut d’Oncologia and Universitat Autonoma of Barcelona, Barcelona, Spain.