Therapeutic advances in small cell lung cancer

Small cell lung cancer (SCLC) is characterised by neuroendocrine differenti ation, early metastatic potential and initial responsiveness to cytotoxic t herapy. Unfortunately, despite recent therapeutic advances, most patients r elapse and the overall five-year survival rate is only 5%. Standard treatme nt of SCLC consists of platinum-based combination chemotherapy, with thorac ic irradiation added for patients with limited-stage disease. Several newer chemotherapeutic drugs have recently been shown to have significant activi ty in patients with untreated or relapsed SCLC. These agents include: the t opoisomerase I inhibitors, topotecan and irinotecan; the taxanes, paclitaxe l and docetaxel; the pyrimidine analogue, gemcitabine; and the vinca alkalo id, vinorelbine. Recent advances in our understanding of the molecular even ts involved in the pathogenesis and progression of SCLC have led to the ide ntification of a variety of potential targets for novel therapeutic intenre ntions. Strategies aimed at inhibiting the myriad of growth factor pathways that. control the proliferation of SCLC cells, include: broad spectrum neu ropeptide antagonists (e.g., substance P analogues); growth factor/receptor -specific inhibitors (e.g., anti-GRP monoclonal antibodies, bradykinin anta gonist dimers); and a variety of selective protein kinase inhibitors. The i mportance of cell death pathways in carcinogenesis and treatment-resistance has led to several novel strategies targeting apoptotic mediators, such as bcl-2, that are frequently dysregulated in SCLC (e.g., bcl-2 antisense). O ur current challenges are to further refine these promising therapeutic str ategies, efficiently evaluate their activity in the clinical setting and in tegrate them into more effective treatment regimens to improve the overall prognosis of patients with SCLC.