title: Chemotherapy-induced peripheral neurotoxicity and ototoxicity: new paradigms for translational genomics.
abstract: In view of advances in early detection and treatment, the 5-year relative survival rate for all cancer patients combined is now approximately 66%. As a result, there are more than 13.7 million cancer survivors in the United States, with this number increasing by 2% annually. For many patients, improvements in survival have been countered by therapy-associated adverse effects that may seriously impair long-term functional status, workplace productivity, and quality of life. Approximately 20% to 40% of cancer patients given neurotoxic chemotherapy develop chemotherapy-induced peripheral neurotoxicity (CIPN), which represents one of the most common and potentially permanent nonhematologic side effects of chemotherapy. Permanent bilateral hearing loss and/or tinnitus can result from several ototoxic therapies, including cisplatin- or carboplatin-based chemotherapy. CIPN and ototoxicity represent important challenges because of the lack of means for effective prevention, mitigation, or a priori identification of high-risk patients, and few studies have applied modern genomic approaches to understand underlying mechanisms/pathways. Translational genomics, including cell-based models, now offer opportunities to make inroads for the first time to develop preventive and interventional strategies for CIPN, ototoxicity, and other treatment-related complications. This commentary provides current perspective on a successful research strategy, with a focus on cisplatin, developed by an experienced, transdisciplinary group of researchers and clinicians, representing pharmacogenomics, statistical genetics, neurology, hearing science, medical oncology, epidemiology, and cancer survivorship. Principles outlined herein are applicable to the construction of research programs in translational genomics with strong clinical relevance and highlight unprecedented opportunities to understand, prevent, and treat long-term treatment-related morbidities.
authors.affiliation: Affiliations of authors: Rubin Center for Cancer Survivorship and Department of Radiation Oncology (LBT) and Department of Neurology (DNH), University of Rochester Medical Center, Rochester, NY; Department of Oncology, Oslo University Hospital, Radiumhospital, Oslo, Norway (SDF); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (HDS); Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (CJB); Department of Chemical and Biomedical Engineering, University of South Florida, Tampa, FL (RDF); Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (DRF); Department of Genitourinary Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX (LCP); Department of Radiation Oncology, Mayo Clinic, Rochester, MN (RCM); Department of Medicine, University of Pennsylvania, Philadelphia, PA (DJV); Department of Medical Oncology, Indiana University, Indianapolis, IN (LHE); Departments of Human Genetics (NJC) and Medicine (MED), University of Chicago, Chicago, IL. lois_travis@urmc.rochester.edu.
authors.forename: Lois B
authors.initials: LB
authors.lastname: Travis
authors.affiliation: Affiliations of authors: Rubin Center for Cancer Survivorship and Department of Radiation Oncology (LBT) and Department of Neurology (DNH), University of Rochester Medical Center, Rochester, NY; Department of Oncology, Oslo University Hospital, Radiumhospital, Oslo, Norway (SDF); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (HDS); Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (CJB); Department of Chemical and Biomedical Engineering, University of South Florida, Tampa, FL (RDF); Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (DRF); Department of Genitourinary Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX (LCP); Department of Radiation Oncology, Mayo Clinic, Rochester, MN (RCM); Department of Medicine, University of Pennsylvania, Philadelphia, PA (DJV); Department of Medical Oncology, Indiana University, Indianapolis, IN (LHE); Departments of Human Genetics (NJC) and Medicine (MED), University of Chicago, Chicago, IL.
authors.forename: Sophie D
authors.initials: SD
authors.lastname: Fossa
authors.affiliation: Affiliations of authors: Rubin Center for Cancer Survivorship and Department of Radiation Oncology (LBT) and Department of Neurology (DNH), University of Rochester Medical Center, Rochester, NY; Department of Oncology, Oslo University Hospital, Radiumhospital, Oslo, Norway (SDF); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (HDS); Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (CJB); Department of Chemical and Biomedical Engineering, University of South Florida, Tampa, FL (RDF); Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (DRF); Department of Genitourinary Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX (LCP); Department of Radiation Oncology, Mayo Clinic, Rochester, MN (RCM); Department of Medicine, University of Pennsylvania, Philadelphia, PA (DJV); Department of Medical Oncology, Indiana University, Indianapolis, IN (LHE); Departments of Human Genetics (NJC) and Medicine (MED), University of Chicago, Chicago, IL.
authors.forename: Howard D
authors.initials: HD
authors.lastname: Sesso
authors.affiliation: Affiliations of authors: Rubin Center for Cancer Survivorship and Department of Radiation Oncology (LBT) and Department of Neurology (DNH), University of Rochester Medical Center, Rochester, NY; Department of Oncology, Oslo University Hospital, Radiumhospital, Oslo, Norway (SDF); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (HDS); Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (CJB); Department of Chemical and Biomedical Engineering, University of South Florida, Tampa, FL (RDF); Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (DRF); Department of Genitourinary Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX (LCP); Department of Radiation Oncology, Mayo Clinic, Rochester, MN (RCM); Department of Medicine, University of Pennsylvania, Philadelphia, PA (DJV); Department of Medical Oncology, Indiana University, Indianapolis, IN (LHE); Departments of Human Genetics (NJC) and Medicine (MED), University of Chicago, Chicago, IL.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Frisina
authors.affiliation: Affiliations of authors: Rubin Center for Cancer Survivorship and Department of Radiation Oncology (LBT) and Department of Neurology (DNH), University of Rochester Medical Center, Rochester, NY; Department of Oncology, Oslo University Hospital, Radiumhospital, Oslo, Norway (SDF); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (HDS); Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (CJB); Department of Chemical and Biomedical Engineering, University of South Florida, Tampa, FL (RDF); Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (DRF); Department of Genitourinary Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX (LCP); Department of Radiation Oncology, Mayo Clinic, Rochester, MN (RCM); Department of Medicine, University of Pennsylvania, Philadelphia, PA (DJV); Department of Medical Oncology, Indiana University, Indianapolis, IN (LHE); Departments of Human Genetics (NJC) and Medicine (MED), University of Chicago, Chicago, IL.
authors.forename: David N
authors.initials: DN
authors.lastname: Herrmann
authors.affiliation: Affiliations of authors: Rubin Center for Cancer Survivorship and Department of Radiation Oncology (LBT) and Department of Neurology (DNH), University of Rochester Medical Center, Rochester, NY; Department of Oncology, Oslo University Hospital, Radiumhospital, Oslo, Norway (SDF); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (HDS); Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (CJB); Department of Chemical and Biomedical Engineering, University of South Florida, Tampa, FL (RDF); Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (DRF); Department of Genitourinary Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX (LCP); Department of Radiation Oncology, Mayo Clinic, Rochester, MN (RCM); Department of Medicine, University of Pennsylvania, Philadelphia, PA (DJV); Department of Medical Oncology, Indiana University, Indianapolis, IN (LHE); Departments of Human Genetics (NJC) and Medicine (MED), University of Chicago, Chicago, IL.
authors.forename: Clair J
authors.initials: CJ
authors.lastname: Beard
authors.affiliation: Affiliations of authors: Rubin Center for Cancer Survivorship and Department of Radiation Oncology (LBT) and Department of Neurology (DNH), University of Rochester Medical Center, Rochester, NY; Department of Oncology, Oslo University Hospital, Radiumhospital, Oslo, Norway (SDF); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (HDS); Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (CJB); Department of Chemical and Biomedical Engineering, University of South Florida, Tampa, FL (RDF); Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (DRF); Department of Genitourinary Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX (LCP); Department of Radiation Oncology, Mayo Clinic, Rochester, MN (RCM); Department of Medicine, University of Pennsylvania, Philadelphia, PA (DJV); Department of Medical Oncology, Indiana University, Indianapolis, IN (LHE); Departments of Human Genetics (NJC) and Medicine (MED), University of Chicago, Chicago, IL.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Feldman
authors.affiliation: Affiliations of authors: Rubin Center for Cancer Survivorship and Department of Radiation Oncology (LBT) and Department of Neurology (DNH), University of Rochester Medical Center, Rochester, NY; Department of Oncology, Oslo University Hospital, Radiumhospital, Oslo, Norway (SDF); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (HDS); Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (CJB); Department of Chemical and Biomedical Engineering, University of South Florida, Tampa, FL (RDF); Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (DRF); Department of Genitourinary Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX (LCP); Department of Radiation Oncology, Mayo Clinic, Rochester, MN (RCM); Department of Medicine, University of Pennsylvania, Philadelphia, PA (DJV); Department of Medical Oncology, Indiana University, Indianapolis, IN (LHE); Departments of Human Genetics (NJC) and Medicine (MED), University of Chicago, Chicago, IL.
authors.forename: Lance C
authors.initials: LC
authors.lastname: Pagliaro
authors.affiliation: Affiliations of authors: Rubin Center for Cancer Survivorship and Department of Radiation Oncology (LBT) and Department of Neurology (DNH), University of Rochester Medical Center, Rochester, NY; Department of Oncology, Oslo University Hospital, Radiumhospital, Oslo, Norway (SDF); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (HDS); Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (CJB); Department of Chemical and Biomedical Engineering, University of South Florida, Tampa, FL (RDF); Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (DRF); Department of Genitourinary Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX (LCP); Department of Radiation Oncology, Mayo Clinic, Rochester, MN (RCM); Department of Medicine, University of Pennsylvania, Philadelphia, PA (DJV); Department of Medical Oncology, Indiana University, Indianapolis, IN (LHE); Departments of Human Genetics (NJC) and Medicine (MED), University of Chicago, Chicago, IL.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Miller
authors.affiliation: Affiliations of authors: Rubin Center for Cancer Survivorship and Department of Radiation Oncology (LBT) and Department of Neurology (DNH), University of Rochester Medical Center, Rochester, NY; Department of Oncology, Oslo University Hospital, Radiumhospital, Oslo, Norway (SDF); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (HDS); Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (CJB); Department of Chemical and Biomedical Engineering, University of South Florida, Tampa, FL (RDF); Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (DRF); Department of Genitourinary Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX (LCP); Department of Radiation Oncology, Mayo Clinic, Rochester, MN (RCM); Department of Medicine, University of Pennsylvania, Philadelphia, PA (DJV); Department of Medical Oncology, Indiana University, Indianapolis, IN (LHE); Departments of Human Genetics (NJC) and Medicine (MED), University of Chicago, Chicago, IL.
authors.forename: David J
authors.initials: DJ
authors.lastname: Vaughn
authors.affiliation: Affiliations of authors: Rubin Center for Cancer Survivorship and Department of Radiation Oncology (LBT) and Department of Neurology (DNH), University of Rochester Medical Center, Rochester, NY; Department of Oncology, Oslo University Hospital, Radiumhospital, Oslo, Norway (SDF); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (HDS); Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (CJB); Department of Chemical and Biomedical Engineering, University of South Florida, Tampa, FL (RDF); Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (DRF); Department of Genitourinary Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX (LCP); Department of Radiation Oncology, Mayo Clinic, Rochester, MN (RCM); Department of Medicine, University of Pennsylvania, Philadelphia, PA (DJV); Department of Medical Oncology, Indiana University, Indianapolis, IN (LHE); Departments of Human Genetics (NJC) and Medicine (MED), University of Chicago, Chicago, IL.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Einhorn
authors.affiliation: Affiliations of authors: Rubin Center for Cancer Survivorship and Department of Radiation Oncology (LBT) and Department of Neurology (DNH), University of Rochester Medical Center, Rochester, NY; Department of Oncology, Oslo University Hospital, Radiumhospital, Oslo, Norway (SDF); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (HDS); Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (CJB); Department of Chemical and Biomedical Engineering, University of South Florida, Tampa, FL (RDF); Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (DRF); Department of Genitourinary Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX (LCP); Department of Radiation Oncology, Mayo Clinic, Rochester, MN (RCM); Department of Medicine, University of Pennsylvania, Philadelphia, PA (DJV); Department of Medical Oncology, Indiana University, Indianapolis, IN (LHE); Departments of Human Genetics (NJC) and Medicine (MED), University of Chicago, Chicago, IL.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.affiliation: Affiliations of authors: Rubin Center for Cancer Survivorship and Department of Radiation Oncology (LBT) and Department of Neurology (DNH), University of Rochester Medical Center, Rochester, NY; Department of Oncology, Oslo University Hospital, Radiumhospital, Oslo, Norway (SDF); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (HDS); Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (CJB); Department of Chemical and Biomedical Engineering, University of South Florida, Tampa, FL (RDF); Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (DRF); Department of Genitourinary Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX (LCP); Department of Radiation Oncology, Mayo Clinic, Rochester, MN (RCM); Department of Medicine, University of Pennsylvania, Philadelphia, PA (DJV); Department of Medical Oncology, Indiana University, Indianapolis, IN (LHE); Departments of Human Genetics (NJC) and Medicine (MED), University of Chicago, Chicago, IL.
authors.forename: M Eileen
authors.initials: ME
authors.lastname: Dolan
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D055106:Genome-Wide Association Study; D023281:Genomics; D006801:Humans; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000235:genetics*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000235:genetics*; D016032:Randomized Controlled Trials as Topic; D057170:Translational Research, Biomedical
chemical_list: D000970:Antineoplastic Agents