Pharmacogenomics of cisplatin sensitivity in non-small cell lung cancer

Abstract

Cisplatin, a platinum-based chemotherapeutic drug, has been used for over 30 years in a wide variety of cancers with varying degrees of success. In particular, cisplatin has been used to treat late stage non-small cell lung cancer (NSCLC) as the standard of care. However, therapeutic outcomes vary from patient to patient. Considerable efforts have been invested to identify biomarkers that can be used to predict cisplatin sensitivity in NSCLC. Here we reviewed current evidence for cisplatin sensitivity biomarkers in NSCLC. We focused on several key pathways, including nucleotide excision repair, drug transport and metabolism. Both expression and germline DNA variation were evaluated in these key pathways. Current evidence suggests that cisplatin-based treatment could be improved by the use of these biomarkers.

Keywords: Biomarker; Cisplatin; Copper transport; Glutathione S-transferase; Non-small cell lung cancer; Nucleotide excision repair.

Figure 1

Schematic diagram of cisplatin’s mechanism of action The three representative pathways discussed in the text are illustrated, including drug action, uptake and metabolism. ATP7A and ATP7B, ATPase, copper transporting, alpha polypeptides A and B; CTR1 and CTR2, copper transporters 1 and 2; ERCC1, excision repair cross-complementation group 1; GSTM1 and P1, glutathione S-transferases Mu 1 and pi 1; XPA, XPD and XDF, xeroderma pigmentosum complementation groups A, D and F.