How could pharmacogenomics help improve patient survival?

Increasing knowledge regarding multiple genetic disturbances found in human lung cancers, particularly non-small cell lung cancer (NSCLC), have enabled predictive markers to be used in specialised centres in tailoring chemotherapy regimens and improving survival and response in subgroups of patients. Impressive responses are observed in patients with epidermal growth factor receptor (EGFR) tyrosine kinase mutations following treatment with gefitinib and erlotinib; and methylation of the mitotic checkpoint gene 14-3-3sigma in circulating tumour serum DNA predicts response to cisplatin/gemcitabine therapy. Expression of markers of DNA repair, ERCC1, RRM1 and BRCA1 are also determinants of response to cisplatin/gemcitabine, with low levels of mRNA predicting improved survival. Patients harbouring the Met/Met mutation in XRCC3 240 have significantly better survival compared with other mutations. These findings are presented in this article, as well as their relevance in customising chemotherapy - illustrated by a hypothetical model guiding treatment decisions in the management of NSCLC.