Targeted therapy in non-small-cell lung cancer--is it becoming a reality?
Treatment outcomes in advanced or metastatic non-small-cell lung cancer (NSCLC) remain unsatisfactory, with low long-term survival rates. Palliative chemotherapy offers a median survival not exceeding 1 year. To date, various combinations of cytotoxic drugs have not improved treatment results beyond what has been observed with platinum doublets. By contrast, molecular targeted drugs may block important pathways that drive cancer progression and achieve long-term disease control. Conflicting results have demonstrated marginal benefit with EGFR inhibitors, anti-EGFR monoclonal antibodies and antiangiogenic strategies in unselected populations of patients with advanced NSCLC. However, patients with an EGFR mutation are likely to respond to agents that target this gene. Novel targeted therapies that interfere with insulin-like growth factor 1 receptor, or the EML4-ALK fusion protein have shown promising activity. Aberrations in other key signaling pathways and molecules, such as RAS/RAF/MEK, PI3K/AKT/mTOR, or MET kinase, have been identified as crucial targets, especially in resistant patients. Novel drugs aimed at these abnormalities are already in the clinic. This Review outlines the current state-of-the-art research for targeted therapy in NSCLC.
Janku
Filip
F
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. fjanku@mdanderson.org
Stewart
David J
DJ
Kurzrock
Razelle
R
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors