AIMS: Individualization of cancer chemotherapy based on the patient's genetic makeup holds promise for reducing side effects and improving efficacy. However, the relative contribution of genetics to drug response is unknown. MATERIALS & METHODS: In this study, we investigated the cytotoxic effect of 29 commonly prescribed chemotherapeutic agents from diverse drug classes on 125 lymphoblastoid cell lines derived from 14 extended families. RESULTS: The results of this systematic study highlight the variable role that genetics plays in response to cytotoxic drugs, ranging from a heritability of <0.15 for gemcitabine to >0.60 for epirubicin. CONCLUSION: Putative quantitative trait loci for cytotoxic response were identified, as well as drug class-specific signatures, which could indicate possible shared genetic mechanisms. In addition to the identification of putative quantitative trait locis, the results of this study inform the prioritization of chemotherapeutic drugs with a sizable genetic response component for future investigation.
AIMS: Individualization of cancer chemotherapy based on the patient's genetic makeup holds promise for reducing side effects and improving efficacy. However, the relative contribution of genetics to drug response is unknown. MATERIALS & METHODS: In this study, we investigated the cytotoxic effect of 29 commonly prescribed chemotherapeutic agents from diverse drug classes on 125 lymphoblastoid cell lines derived from 14 extended families. RESULTS: The results of this systematic study highlight the variable role that genetics plays in response to cytotoxic drugs, ranging from a heritability of <0.15 for gemcitabine to >0.60 for epirubicin. CONCLUSION: Putative quantitative trait loci for cytotoxic response were identified, as well as drug class-specific signatures, which could indicate possible shared genetic mechanisms. In addition to the identification of putative quantitative trait locis, the results of this study inform the prioritization of chemotherapeutic drugs with a sizable genetic response component for future investigation.
Authors: Vivian G Cheung; Laura K Conlin; Teresa M Weber; Melissa Arcaro; Kuang-Yu Jen; Michael Morley; Richard S Spielman Journal: Nat Genet Date: 2003-02-03 Impact factor: 38.330
Authors: Mark J Ratain; Antonius A Miller; Howard L McLeod; Alan P Venook; Merrill J Egorin; Richard L Schilsky Journal: Clin Cancer Res Date: 2006-06-01 Impact factor: 12.531
Authors: James W Watters; Aldi Kraja; Melissa A Meucci; Michael A Province; Howard L McLeod Journal: Proc Natl Acad Sci U S A Date: 2004-07-28 Impact factor: 11.205
Authors: Shiwei Duan; Wasim K Bleibel; Rong Stephanie Huang; Sunita J Shukla; Xiaolin Wu; Judith A Badner; M Eileen Dolan Journal: Cancer Res Date: 2007-06-01 Impact factor: 12.701
Authors: Edwin Choy; Roman Yelensky; Sasha Bonakdar; Robert M Plenge; Richa Saxena; Philip L De Jager; Stanley Y Shaw; Cara S Wolfish; Jacqueline M Slavik; Chris Cotsapas; Manuel Rivas; Emmanouil T Dermitzakis; Ellen Cahir-McFarland; Elliott Kieff; David Hafler; Mark J Daly; David Altshuler Journal: PLoS Genet Date: 2008-11-28 Impact factor: 5.917
Authors: John Jack; Tammy M Havener; Howard L McLeod; Alison A Motsinger-Reif; Matthew Foster Journal: Pharmacogenomics Date: 2015-08-28 Impact factor: 2.533
Authors: J Jack; G W Small; C C Brown; T M Havener; H L McLeod; A A Motsinger-Reif; K L Richards Journal: Pharmacogenomics J Date: 2017-12-05 Impact factor: 3.550
Authors: Chad C Brown; Tammy M Havener; Marisa W Medina; John R Jack; Ronald M Krauss; Howard L McLeod; Alison A Motsinger-Reif Journal: Pharmacogenomics Date: 2014-02 Impact factor: 2.533
Authors: Uchenna O Njiaju; Eric R Gamazon; Lidija K Gorsic; Shannon M Delaney; Heather E Wheeler; Hae Kyung Im; M Eileen Dolan Journal: Pharmacogenet Genomics Date: 2012-07 Impact factor: 2.089
Authors: Lara Sánchez-Barroso; Maria Apellaniz-Ruiz; Gerardo Gutiérrez-Gutiérrez; María Santos; Juan M Roldán-Romero; Maria Curras; Laura Remacha; Bruna Calsina; Isabel Calvo; María Sereno; María Merino; Jesús García-Donas; Beatriz Castelo; Eva Guerra; Rocio Letón; Cristina Montero-Conde; Alberto Cascón; Lucía Inglada-Pérez; Mercedes Robledo; Cristina Rodríguez-Antona Journal: Oncologist Date: 2018-11-23
Authors: Aparna Chhibber; Deanna L Kroetz; Kelan G Tantisira; Michael McGeachie; Cheng Cheng; Robert Plenge; Eli Stahl; Wolfgang Sadee; Marylyn D Ritchie; Sarah A Pendergrass Journal: Pharmacogenomics Date: 2014-12 Impact factor: 2.533
Authors: Hemant Kulkarni; Harald H H Göring; Joanne E Curran; Vincent Diego; Thomas D Dyer; Shelley Cole; Ken R Walder; Greg R Collier; John Blangero; Melanie A Carless Journal: Cancer Chemother Pharmacol Date: 2013-02-19 Impact factor: 3.333
Authors: Chad C Brown; Tammy M Havener; Marisa W Medina; J Todd Auman; Lara M Mangravite; Ronald M Krauss; Howard L McLeod; Alison A Motsinger-Reif Journal: Pharmacogenet Genomics Date: 2012-11 Impact factor: 2.089