Despite many clinical efforts, non-small-cell lung cancer (NSCLC) has a dismal 5-year survival rate of 16%, and high incidence of recurrence. The success of biologically targeted agents, as well as the activity of well-established chemotherapeutic regimens, has been limited by inherited/acquired resistance, and biomarkers to adapt the prescription of anticancer drugs to patients' features are urgently warranted. Areas covered. In oncology, pharmacogenetics should provide the way to select patients who may benefit from a specific therapy that best match the individual and tumor genetic profile, thus allowing maximum activity and minimal toxicity. The present review summarizes the main findings on NSCLC pharmacogenetics, critically reappraising the most important studies on polymorphisms correlated with outcome of pemetrexed and EGFR-inhibitors, and provides perspective on clinical application of genomic tests for treatment decision-making. Expert Opinion. A major challenge in NSCLC is the identification of subgroups of diseases/patients that will truly benefit from specific treatments. Ideally, convenient and minimally invasive tests to decipher biomarkers of chemosensitivity/resistance and toxicity should be developed alongside novel anticancer treatments. Integration with the latest generation of whole-genome analyses and liquid biopsies as well as prospective validation in large cohorts of patients will overcome the limitations of the traditional pharmacogenetic approaches.
Keywords: EGFR inhibitors; lung cancer; methodological challenges; pemetrexed; pharmacogenetic studies.