Oncogenes and Tumor Suppressor Genes in Small Cell Lung Carcinoma

Small cell lung cancer (SCLC) makes up almost 15% of all cases of lung cancer and occurs almost exclusively in individuals with a history of smoking (Blackhall & Faivre-Finn, 2011; Meyerson et al., 2004; Tamasi and Muller, 2011; Walenkamp et al., 2009). However, SCLCs differ significantly from NSCLCs in specific genetic alterations that occur. Moreover, smoking-damaged bronchial epithelia accompanying SCLCs appears to have undergone significantly more acquired genetic damage than is frequently found in NSCLCs. Two subtypes of SCLC exist: homogeneous small cell carcinoma and combined SCLC (mixture of any non-small cell type) (Meyerson et al., 2004; Tamasi and Muller, 2011). SCLC in its advanced stage has an aggressive clinical course and is commonly accompanied by paraneoplastic syndromes. Autocrine growth factors, such as neuroendocrine regulatory peptides (e.g. bombesin/gastrin-releasing peptide), are prominent in SCLC. SCLC is categorized as limited stage disease (LS) when confined to the ipsilateral hemithorax and within a single radiation port, while extensive stage disease (ES) includes metastatic disease outside the ipsilateral hemithorax (Blackhall & Faivre-Finn, 2011; Meyerson et al., 2004; Tamasi and Muller, 2011; Walenkamp et al., 2009). SCLC is sensitive to chemotherapy; response rates to front-line agents are often in the range of 60%, with approximately 10% of patients achieving a complete response, even in the setting of metastatic disease (Brambilla et al., 2009 Jemal et al., 2006). Despite this, the relapse rates are quite high and survival with currently available salvage therapy is quite modest. With current therapy, patients with LSSCLC have a median survival of 17 months and a 5-year overall survival rate of 12% , while patients with ES-SCLC have a median survival of 8.9 months, and a 5-year survival rate of approximately 2%. (Brambilla et al., 2009 Jemal et al., 2006; Tamasi and Muller, 2011). This article will review the molecular targeted agents, the genetic abnormalities, and therapeutic efficacy in SCLC.