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Abstract
Cancer patients exhibit a wide heterogeneity in their responses to chemotherapy. Improvement in chemotherapeutic responses could be achieved by gaining more detailed information on the molecular determinants (i.e., DNA, RNA or protein) underlying this heterogeneity. Pharmacogenomics approaches can be used to integrate information on drug responsiveness with alterations in molecular entities, often on a genome-wide scale. By using information gleaned from pharmacogenomics studies, it is anticipated that cancer chemotherapy can be tailored to the individual patient or tumor phenotype. This review focuses on pharmacogenomics studies conducted to gain insight into the molecular determinants of chemosensitivity to cancer chemotherapeutics.
| ABBREVIATIONS | ||
| ABCB1/MDR1: | = | ATP-binding cassette, sub-family B, member 1/ multidrug resistance 1 |
| ALL: | = | acute lymphoblastic leukemia |
| ASNS: | = | asparagine synthetase |
| CEPH: | = | Centre d'Etude du Polymorphisme Humain |
| CYP2D6: | = | cytochrome P450, family 2, subfamily D, polypeptide 6 |
| DNA: | = | deoxyribonucleic acid |
| DPYD: | = | dihydropyrimidine dehydrogenase |
| EGFR: | = | epidermal growth factor receptor |
| ERBB2: | = | v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glio blastoma derived oncogene homolog |
| FDA: | = | Food and Drug Administration |
| 5-FU: | = | 5-fluorouracil |
| GSTM1: | = | glutathione S-transferase M1 |
| mRNA: | = | messenger ribonucleic acid |
| MTHFR: | = | 5,10-methylenetetrahydrofolate reductase |
| NCI: | = | National Cancer Institute |
| NSCLC: | = | non-small cell lung cancer |
| RNA: | = | ribonucleic acid |
| RT-PCR: | = | reverse transcriptase – polymerase chain reaction |
| SNPs: | = | single nucleotide polymorphisms |
| TAILORx: | = | Trial Assigning Individualized Options for Treatment |
| TYMS: | = | thymidylate synthetase |
Acknowledgments
The authors are supported in part by NIH grants U01 GM63340, P50 CA106991, and P30 CA016086.