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.

KEYWORDS::

• chemotherapy
• genotype–phenotype association
• novel methodologies
• NSCLC
• pharmacogenetics
• prospective studies

Financial & competing interests disclosure

This work was partially funded by grants from The Netherlands Organisation for Scientific Research (NWO; Veni grant) and AIRC Marie Curie International Fellowship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was partially funded by grants from The Netherlands Organisation for Scientific Research (NWO; Veni grant) and AIRC Marie Curie International Fellowship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.