Pharmacogenomic approaches to individualizing chemotherapy for non-small-cell lung cancer: current status and new directions.
At present, selection of chemotherapy regimens for individual patients remains largely an empirical process. Nevertheless, developing pharmacogenomic approaches for selection of chemotherapy through predictive biomarkers now appears feasible because of improved understanding of underlying molecular mechanisms. Although diverse terminology has been applied to such pharmacogenomic approaches (individualizing, customizing, or personalizing therapy), all rely on commonly shared principles for assessing tumor- or host-related factors. Herein, we summarize emerging data regarding pharmacogenomic approaches to treatment selection for non-small-cell lung cancer, focusing primarily on biomarkers relevant to 2 important chemotherapeutic drug classes: platinum compounds and antimicrotubule agents. The results of pilot studies and the first randomized prospective trial testing this concept are described, including limitations in the clinical setting of advanced-stage disease. Methodologic and technical aspects of pharmacogenomic approaches are elucidated, recommendations for clinical application are provided, and new directions in this field are projected.
Gautschi
Oliver
O
Department of Medical Oncology, Bern University Hospital, Bern, Switzerland.
Mack
Philip C
PC
Davies
Angela M
AM
Jablons
David M
DM
Rosell
Rafael
R
Gandara
David R
DR
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D016190:Carboplatin / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004720:Endonucleases / Q000235:genetics; D019398:Genes, BRCA1; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010597:Pharmacogenetics; D011379:Prognosis; D043823:Taxoids / Q000627:therapeutic use; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D043823:Taxoids; D003841:Deoxycytidine; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D000093542:Gemcitabine