Molecular predictors of EGFR-TKI sensitivity in advanced non-small cell lung cancer.
The epidermal growth factor receptor (EGFR) is overexpressed in the majority of non-small cell lung cancers (NSCLC) and is a major target for new therapies. Specific EGFR tyrosine kinase inhibitors (TKIs) have been developed and used for the treatment of advanced NSCLC. The clinical response, however, varies dramatically among different patient cohorts. Females, East Asians, non-smokers, and patients with adenocarcinoma usually show higher response rates. Meanwhile, a number of biological factors are also associated with EGFR-TKIs responsiveness. In order to better understand the predictive value of these biomarkers and their significance in clinical application we prepared this brief review. Here we mainly focused on EGFR somatic mutations, MET amplification, K-ras mutations, EGFRvIII mutation, EGFR gene dosage and expression, HER2 gene dosage and expression, and Akt phosphorylation. We think EGFR somatic mutation probably is the most effective molecular predictor for EGFR-TKIs responsiveness and efficacy. Mutation screening test can provide the most direct and valuable guidance for clinicians to make decision on EGFR-TKIs therapy.
Zhang
Xiaozhu
X
International Medical Centre, Johns Hopkins Singapore, Singapore. xiaozhu@imc.jhmi.edu
Chang
Alex
A
D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors