Biological heterogeneity of small cell lung cancer

Abstract

Over the past 20 years considerable advances have been made in the characterization of the biologic properties of small cell lung cancer. The recognition that this histologic type of lung cancer, in contrast to the other major types of lung cancer, is highly sensitive to both chemotherapy and radiation therapy lead to significant improvements in the overall survival of patients with this disease. However, in spite of the initial major advances in therapy, overall results and survival have remained unchanged over the past 5 years. The majority of patients, although they will demonstrate an initial response to cytotoxic therapy, will ultimately die of their disease due to the development of drug resistance. Whether this development of drug resistance within a tumor cell represents the emergence of resistant clones of cells present at diagnosis, or a change within the cells exposed to cytotoxic therapy that renders them resistant to further therapy remains to be determined. The development of laboratory techniques that facilitate the culture and establishment of SCLC cell lines has greatly improved our understanding of the biology of SCLC, in addition to providing useful models for studies of mechanisms of drug resistance and metabolism. The ease of establishment of SCLC cell lines in defined medium suggests that these cells secrete "autocrine growth factors" essential for their growth in vitro. The characterization of these factors may provide an alternative means for treating this tumor in vivo. Moreover, by developing specific culture media for other types of lung cancer, similar advances in our knowledge of these tumors will occur. Although the growth of SCLC cells in a clonogenic assay may be of value in chemotherapy selection, the established cell lines provide a model for studying mechanisms of drug and radiation sensitivity; and drug metabolism. The recognition that SCLC cell lines have elevated levels of L-dopa decarboxylase has lead to the development of specific agents that may alter the growth of these cells through inhibition of polyamine synthesis. Such specifically designed therapy may become important in the future therapy of these patients. The establishment of cell lines has clearly indicated the considerable heterogeneity that exists in SCLC.(ABSTRACT TRUNCATED AT 400 WORDS)