'Toxgnostics': an unmet need in cancer medicine.
If we were to summarize the rationale that underpins medical oncology in a Latin aphorism, it might be 'veneno ergo sum'; that is, I poison, therefore I am. The burden of chemotherapy-associated toxicity is well recognized, but we have relatively few tools that increase the precision of anticancer drug prescribing. We propose a shift in emphasis from the focussed study of polymorphisms in drug metabolic pathways in small sets of patients to broader agnostic analyses to systematically correlate germline genetic variants with adverse events in large, well-defined cancer populations. Thus, we propose the new science of 'toxgnostics' (that is, the systematic, agnostic study of genetic predictors of toxicity from anticancer therapy).
1] Oxford Cancer Centre, Department of Oncology, University of Oxford, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE, UK. [2] Molecular and Population Genetics Laboratory, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.
David
D
Church
Oxford Cancer Centre, Department of Oncology, University of Oxford, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE, UK.
Rachel
R
Kerr
Molecular and Population Genetics Laboratory, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.
Enric
E
Domingo
Molecular and Population Genetics Laboratory, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.
Dan
D
Rosmarin
Molecular and Population Genetics Laboratory, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.
Claire
C
Palles
Oxford Cancer Biomarkers, The Magdalen Centre, Oxford Science Park, Robert Robinson Avenue, Oxford, OX4 4GA, UK.
Kevin
K
Maskell
1] Molecular and Population Genetics Laboratory, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK. [2] Genomic Medicine Theme, Oxford Comprehensive Biomedical Research Centre, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.
Ian
I
Tomlinson
Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK.
David
D
Kerr
D000970:Antineoplastic Agents / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000235:genetics*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins