MedicalResearch.com Interview with:
Prof. Gerhard Hamilton
Department of Obstetrics and Gynecology
Medical University of Vienna
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Small cell lung cancer (SCLC) is a highly aggressive tumor (15 % of all lung cancers) mainly of patients with high tobacco consumption which shows an extremely poor survival (< 5% 2-year survival rate). Unfortunately the
low survival rates of advanced SCLC cases has not improved significantly during the last decades, with platinum drugs/etoposide and topotecan employed for first- and second-line chemotherapy, respectively. All kinds of new chemotherapeutics, targeted drugs and immunotherapies either failed or resulted in prolongation of survival of several months at best. SCLC responds well to first-line therapy but relapses within a short time as chemoradioresistant tumor. The failure of hundreds of registered studies seem to be linked to the lack of knowledge of the mechanism of resistance of SCLCs and proper ways to reverse the refractoriness.
Small cell lung cancer is distinguished by excessive numbers of circulating tumor cells (CTCs) in advanced stages. CTCs contain the founder of metastasis and seem to constitute a highly chemoresistant cell population. Thus, we ware able to establish a panel of permanent CTC lines in vitro for the first time (8 SCLC lines so far from blood samples). Although CTCs were considered to be chemoresistant we detected that they are chemosensitive in vitro in form of single cell suspensions. However, all CTC lines developed spontaneously into large multicellular aggregates, termed tumorospheres, which grow up to 1-2 mm in size and exhibit high chemoradioresistance due to limited drug perfusion as well as content of quiescent and hypoxic cells. Resistance to irradiation seems to be caused by lack of oxygen, such limiting the generation of oxygen radicals. High resistance mediated by the occurrence of tumorospheres easily explains the failure of a large number of drugs – if one is not able to achieve a sufficient concentration of a drug in cancer cells and the cells are quiescent, the respective compounds will not be able to destroy the target cells, regardless of their chemical nature.