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Pharmacogenetics of non-small cell lung cancer (NSCLC): time to "work it out"?

Abstract：

:The disappointing results in long-term survival of patients affected by non-small cell lung cancer (NSCLC) may be attributed, at least in part, to the lack of knowledge on the way by which genetic characteristics in normal and neoplastic cells affect responsiveness as well as metabolism of chemotherapy and new targeted agents. This issue deserves further pharmacogenetics studies, in order to identify patients who are most likely to benefit from specific therapies selected on the base of the individual and tumor genetic features, thus improving the efficacy/toxicity profile of the treatment strategy. Even if most meta-analyses in NSCLC yielded contradictory results, a number of candidate biomarkers for response/resistance to conventional chemotherapeutic agents such as gemcitabine, platinum-compounds, pemetrexed and taxanes have been proposed. Similarly, recent studies suggested the key role of polymorphisms in the prediction of toxicity to EGFR-targeted agents. However, larger prospective randomized trials of personalized therapy to validate these biomarkers are still needed. The unification of the technical procedures, as well as additional investigation to unravel pivotal factors influencing genotype-phenotype relationships, represent other crucial issues. From this perspective, functional studies aiming at unravel eventual pharmacokinetics/pharmacodynamics interactions are critical for the pharmacogenetic optimization of anti-cancer regimens. With the development of high-throughput technologies, including whole exome analyses, the traditional pharmacogenetic approach that till present has relied only on candidate genes suspected of influencing drug response/metabolism can be fulfilled with further lists of potential predictive alleles. The clinical implementation of such pharmacogenetics/genomics studies as well as of therapeutic drug monitoring could enable clinicians to personalize treatment to enhance efficacy and/or limit toxicity.

journal_name

Curr Pharm Des

journal_title

Current pharmaceutical design

authors

Galvani E,Toffalorio F,Peters GJ,De Pas T,Giovannetti E

doi

10.2174/13816128113196660756

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

3863-74

issue

eissn

1381-6128

issn

1873-4286

pii

CPD-EPUB-56740

journal_volume

pub_type

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Pharmacogenetics of non-small cell lung cancer (NSCLC): time to "work it out"?