Small cell lung cancer: a problem of tumor heterogeneity.

Small cell undifferentiated carcinoma represents a subtype of lung cancer that possesses biologic and clinical characteristics that make it significantly distinct from other forms. A major impact on the natural history of this disease has been accomplished during the past 15 years, including the potential for cure by non-surgical treatment modalities. Further progress in the management of this disorder has been impaired by a number of factors that appear to be inherent to the biology of the tumor and its clinical features. Analysis of initial clinical trials and more detailed examination of this tumor in vitro have permitted the elucidation of many barriers to curative outcome presently being evaluated at the laboratory and clinical levels. These include clear biologic and morphologic heterogeneity; problems with chemotherapy responsiveness including drug resistance; the potential for combining chemotherapy and radiation modalities; the re-examination of the role of surgical intervention in selected patients; and the need to deal with central nervous system dissemination of tumor cells. Further advances in this disease will be dependent on the successful integration of laboratory and clinical disciplines.