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.
Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Ctra Canyet, s/n 08916 Badalona (Barcelona), Spain. rrosell@ico.scs.es
Rafael
R
Rosell
Enriqueta
E
Felip
Luis
L
Paz-Ares
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005092:Exonucleases / Q000235:genetics; D005095:Exoribonucleases; D019398:Genes, BRCA1; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D010597:Pharmacogenetics; D012262:Ribonucleoside Diphosphate Reductase; D025521:Tumor Suppressor Proteins / Q000235:genetics
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; C110901:X-ray repair cross complementing protein 3; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D066246:ErbB Receptors; C071447:ERCC1 protein, human; D004720:Endonucleases; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human