Biomarkers of clinical benefit for anti-epidermal growth factor receptor agents in patients with non-small-cell lung cancer

Abstract

Non-small-cell lung cancer (NSCLC) remains by far the major cause of cancer-related death in the Western world in both men and women. The majority of patients will be diagnosed with metastatic disease, and chemotherapy doublets remain the cornerstone of treatment for these patients. However, chemotherapy has a minimal impact on long-term survival and prognosis remains poor for these patients. Further improvement in treatment is likely to require incorporation of novel targeted therapies. Among these agents, inhibitors of the epidermal growth factor receptor (EGFR) have demonstrated significant activity in the first-, second- or third-line treatment of NSCLC. The purpose of current paper is to present the evidence for using several proposed molecular biomarkers as a tool for selection of NSCLC patients for anti-EGFR treatment. According to current data, EGFR mutation status appears to be the strongest predictor for the selection of NSCLC patients to first-line treatment with EGFR tyrosine kinase inhibitors vs chemotherapy. Use of other biomarkers remains investigational.

Role of Fluorescence in situ Hybridization in Lung Cancer Cytology

“…It remains controversial whether EGFR CNG might still have some role in predicting the benefit from EGFR TKIs in an EGFR wild-type population [45]. Overall, FISH testing of NSCLC for EGFR CNG should currently not be used as a selection tool for treatment with EGFR TKIs or cetuximab [19,46,47]. …”

miR-205 Targets PTEN and PHLPP2 to Augment AKT Signaling and Drive Malignant Phenotypes in Non–Small Cell Lung Cancer

“…The overall 5-year survival rate for NSCLC, with all stages and subtypes combined, remains as low as 15% (1). Despite advances in surgical therapy, radiotherapy, chemotherapy, and recently developed targeting therapy such as anti-EGF receptor (EGFR) and anti-VEGF targeting strategies, the mortality of the disease has not been markedly reduced thus far (2,3). The suboptimal efficacies of currently available therapeutic approaches to the treatment of lung cancer are largely attributable to difficulties in dealing with the malignant phenotype of the disease, namely, its highly uncontrolled characteristics of overactivated proliferation, neovascularization, invasiveness, and metastasis supported and/or promoted by deregulated molecular signaling pathways within lung cancer cells (4).…”

miR-186 Downregulation Correlates with Poor Survival in Lung Adenocarcinoma, Where It Interferes with Cell-Cycle Regulation

“…Non-small cell lung carcinoma (NSCLC), which includes squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, large cell carcinoma, and several other histologic types, and is responsible for almost 80% of lung cancer-related deaths, represents the most prevalent histologic subtype of the tumor type (3). Currently available treatment strategies for NSCLC, including surgery, radiotherapy, and chemotherapy, however, remain generally unsuccessful (4). For example, the 5-year survival rate for patients with stage IV NSCLC is only approximately 1%, with the median survival time of 7 months (5).…”

“…For example, the 5-year survival rate for patients with stage IV NSCLC is only approximately 1%, with the median survival time of 7 months (5). Despite incremental advancements in molecular therapeutics for the treatment of NSCLC, such as epithelial growth factor receptor-targeting therapies, patient survival has not been improved significantly, and the disease remains to be a long-term challenge with a dismal prognosis (3)(4)(5)(6). Identification of molecular events key to the carcinogenesis and tumor progression will facilitate development of new therapeutic targets and anti-lung cancer strategies.…”