Impact of biomarkers on non-small cell lung cancer treatment.
Chemotherapy represents the mainstay of non-small cell lung cancer (NSCLC) treatment, but response is usually observed in only one out of three patients. Massive efforts have been carried out to identify biomarkers that might help clinicians to choose appropriate drugs, by identifying potentially sensitive subjects and spare toxicities in patients who are unlikely to benefit from treatment. Low excision repair cross-complementation group 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) levels have been associated with increased sensitivity to cisplatin and gemcitabine, respectively, while reduced class III beta-tubulin expression has been associated with taxane activity. Initial prospective studies showed the feasibility of a customized approach based on biomarker assessment, and phase III trials will hopefully provide further validation of this approach. The impact of biomarkers for patient selection has now been well established for tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR), with EGFR mutations emerging as the most reliable predictor for improved outcome. Relevant clinical issues are represented by the identification of patients who can be reasonably excluded from treatment and by the development of therapeutic approaches able to overcome acquired resistance to anti-EGFR strategies.
Toschi
Luca
L
Dana-Farber Cancer Institute, Boston, MA 02215, USA. luca_toschi@dfci.harvard.edu
Cappuzzo
Federico
F
D000970:Antineoplastic Agents / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D004720:Endonucleases / Q000037:antagonists & inhibitors / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D011379:Prognosis; D012262:Ribonucleoside Diphosphate Reductase; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D004268:DNA-Binding Proteins; C498585:TUBB3 protein, human; D043823:Taxoids; D014404:Tubulin; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; C512478:EGFR protein, human; D066246:ErbB Receptors; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin; D000093542:Gemcitabine