title: A decision support framework for genomically informed investigational cancer therapy.
abstract: Rapidly improving understanding of molecular oncology, emerging novel therapeutics, and increasingly available and affordable next-generation sequencing have created an opportunity for delivering genomically informed personalized cancer therapy. However, to implement genomically informed therapy requires that a clinician interpret the patient's molecular profile, including molecular characterization of the tumor and the patient's germline DNA. In this Commentary, we review existing data and tools for precision oncology and present a framework for reviewing the available biomedical literature on therapeutic implications of genomic alterations. Genomic alterations, including mutations, insertions/deletions, fusions, and copy number changes, need to be curated in terms of the likelihood that they alter the function of a "cancer gene" at the level of a specific variant in order to discriminate so-called "drivers" from "passengers." Alterations that are targetable either directly or indirectly with approved or investigational therapies are potentially "actionable." At this time, evidence linking predictive biomarkers to therapies is strong for only a few genomic markers in the context of specific cancer types. For these genomic alterations in other diseases and for other genomic alterations, the clinical data are either absent or insufficient to support routine clinical implementation of biomarker-based therapy. However, there is great interest in optimally matching patients to early-phase clinical trials. Thus, we need accessible, comprehensive, and frequently updated knowledge bases that describe genomic changes and their clinical implications, as well as continued education of clinicians and patients.
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB). fmeric@mdanderson.org.
authors: Funda
authors: F
authors: Meric-Bernstam
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: Amber
authors: A
authors: Johnson
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: Vijaykumar
authors: V
authors: Holla
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: Ann Marie
authors: AM
authors: Bailey
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: Lauren
authors: L
authors: Brusco
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: Ken
authors: K
authors: Chen
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: Mark
authors: M
authors: Routbort
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: Keyur P
authors: KP
authors: Patel
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: Jia
authors: J
authors: Zeng
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: Scott
authors: S
authors: Kopetz
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: Michael A
authors: MA
authors: Davies
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: Sarina A
authors: SA
authors: Piha-Paul
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: David S
authors: DS
authors: Hong
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: Agda Karina
authors: AK
authors: Eterovic
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: Apostolia M
authors: AM
authors: Tsimberidou
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: Russell
authors: R
authors: Broaddus
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: Elmer V
authors: EV
authors: Bernstam
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: Kenna R
authors: KR
authors: Shaw
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: John
authors: J
authors: Mendelsohn
authors: Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy , the University of Texas MD Anderson Cancer Center, Houston, TX (FMB, AJ, VH, AMB, JZ, KRS, JM, GBM); Departments of Investigational Cancer Therapeutics (FMB, LB, SAPP, DSH, AMT), Surgical Oncology (FMB), Hematopathology (MR, KPP), Bioinformatics & Computational Biology (KC), GI Medical Oncology (SK), Melanoma Medical Oncology (MAD), Experimental Therapeutics (RB), Systems Biology (AKE, GBM), the University of Texas MD Anderson Cancer Center, Houston, TX; School of Biomedical Informatics, the University of Texas Health Science Center, Houston, TX (EVB).
authors: Gordon B
authors: GB
authors: Mills
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics*; D056915:DNA Copy Number Variations; D004273:DNA, Neoplasm / Q000032:analysis; D003661:Decision Support Techniques; D017277:Drug Approval; D015507:Drugs, Investigational / Q000494:pharmacology*; D019317:Evidence-Based Medicine; D017353:Gene Deletion; D020869:Gene Expression Profiling; D050939:Gene Fusion; D023281:Genomics; D018095:Germ-Line Mutation; D006801:Humans; D058990:Molecular Targeted Therapy / Q000639:trends; D016254:Mutagenesis, Insertional; D009154:Mutation / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D057285:Precision Medicine / Q000639:trends*; D011237:Predictive Value of Tests; D017422:Sequence Analysis, DNA; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D015507:Drugs, Investigational