title: Genomically Driven Tumors and Actionability across Histologies: BRAF-Mutant Cancers as a Paradigm.
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 BRAF as 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 suggest BRAF-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); 533-47. ©2016 AACR.
authors.affiliation: CollabRx Inc., San Francisco, California.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Turski
authors.affiliation: CollabRx Inc., San Francisco, California.
authors.forename: Smruti J
authors.initials: SJ
authors.lastname: Vidwans
authors.affiliation: Department of Investigational Cancer Therapeutics - a Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Garrido-Laguna
authors.affiliation: Banner MD Anderson Cancer Center, Gilbert, Arizona.
authors.forename: Javier
authors.initials: J
authors.lastname: Munoz
authors.affiliation: Center for Personalized Cancer Therapy, Moores Cancer Center, University of California, San Diego, California.
authors.forename: Richard
authors.initials: R
authors.lastname: Schwab
authors.affiliation: Department of Investigational Cancer Therapeutics - a Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Vivek
authors.initials: V
authors.lastname: Subbiah
authors.affiliation: Vall d'Hebron Institut d'Oncologia and Universitat Autonoma of Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Rodon
authors.affiliation: Center for Personalized Cancer Therapy, Moores Cancer Center, University of California, San Diego, California. rkurzrock@mail.ucsd.edu.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D014644:Genetic Variation; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf