title: Oncogenic pathways, molecularly targeted therapies, and highlighted clinical trials in non-small-cell lung cancer (NSCLC).
abstract: Non-small-cell lung cancer (NSCLC) has recently been associated with interesting molecular characteristics that have important implications in carcinogenesis and response to targeted therapies. The unsatisfactory treatment outcomes in advanced NSCLC with respect to long-term survival rates may be improved through a better understanding of the molecular etiology of this disease. For instance, several molecular alterations have been defined as "driver mutations," such as mutations in epidermal growth factor receptor (EGFR), Kirsten-rous avian sarcoma (KRAS), and a chromosome 2p inversion producing an EML4-ALK fusion gene (echinoderm microtubule-associated protein-like 4 fused with the anaplastic lymphoma kinase). Other key signaling pathways such as RAS/RAF/MEK, PI3K/AKT/mTOR (mammalian target of rapamycin), mesenchymal-epithelial transition (MET) kinase, LKB1, and insulin-like growth factor 1 (IGF-1) receptor (IGF-1R) have also been identified as novel targets for lung cancer treatment. In this review we focus on the molecular discoveries that have led to the clinical applications and trials of novel targeted agents, including the clinical trials that selectively studied patients who were predicted to achieve the greatest benefit based on the expression of correlative biomarkers.
authors.affiliation: Medical Oncology Division, Department of Internal Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Thanyanan
authors.initials: T
authors.lastname: Reungwetwattana
authors.forename: Saravut J
authors.initials: SJ
authors.lastname: Weroha
authors.forename: Julian R
authors.initials: JR
authors.lastname: Molina
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D002986:Clinical Trials as Topic; D006801:Humans; D008175:Lung Neoplasms / Q000178:diet therapy / Q000235:genetics* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009154:Mutation; D015398:Signal Transduction / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*
chemical_list: D000970:Antineoplastic Agents