title: Pharmacogenetics of conventional chemotherapy in non-small-cell lung cancer: a changing landscape?
abstract: Pharmacogenetics might be used to select patients who may benefit from specific chemotherapy that best matches the individual and tumor genetic profile, thus allowing maximum activity and minimal toxicity. Even if most studies in non-small-cell lung cancer yielded contradictory results, several potential biomarkers for sensitivity/resistance to platinum compounds, gemcitabine, taxanes and pemetrexed have been proposed. However, these markers need to be validated within larger prospective randomized trials of customized chemotherapy in homogeneous populations. Other critical points include the optimization/standardization of technical procedures, and further studies to unravel the extremely complex regulation of gene function. From this perspective, the evaluation of key factors influencing genotype-phenotype relationships, such as miRNAs, and functional studies to clarify pharmacokinetic/pharmacodynamic interactions, are fundamental for the pharmacogenetic optimization of cancer chemotherapy. Finally, limitation of the traditional pharmacogenetic approach relying only on candidate genes suspected of affecting drug response is now being overcome by the use of novel genome-wide studies.
authors: Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors: Elisa
authors: E
authors: Giovannetti
authors: Francesca
authors: F
authors: Toffalorio
authors: Tommaso
authors: T
authors: De Pas
authors: Godefridus J
authors: GJ
authors: Peters
mesh_terms: D054316:Biomarkers, Pharmacological; D016190:Carboplatin / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics; D002945:Cisplatin / Q000627:therapeutic use; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005971:Glutamates / Q000627:therapeutic use; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics; D000068437:Pemetrexed; D010597:Pharmacogenetics / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D043823:Taxoids / Q000627:therapeutic use; D000093542:Gemcitabine
chemical_list: D054316:Biomarkers, Pharmacological; D005971:Glutamates; D043823:Taxoids; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D016190:Carboplatin; D002945:Cisplatin; D000093542:Gemcitabine