期刊
PHARMACOGENOMICS
卷 12, 期 10, 页码 1407-1415出版社
FUTURE MEDICINE LTD
DOI: 10.2217/PGS.11.92
关键词
cancer; cell line; chemotherapy; cytotoxicity; pharmacogenetics; pharmacogenomic; QTL
资金
- NIH Pharmacogenetics Research Network [U01 GM63340]
- NIEHS [2 T32 ES007329]
- University North Carolina
- Triad Golfers Against Cancer
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.
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