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.