Assessing mechanisms of small cell lung cancer drug resistance in circulating tumour cells

Abstract

SCLC is the most aggressive subtype of lung cancer and accounts for 13% of lung cancer diagnoses. Median survival, even with treatment, is under 10 months and 5-year survival is <5%. Most patients are treated with chemotherapy and radiation. The limited role of surgery means few biological specimens are available for research. In the clinic, 70% of patient tumours initially respond to chemotherapy, but almost all will relapse within months with resistant disease. Understanding the mechanism leading to treatment resistance will be important to improving patient outcomes in SCLC. A consequence of SCLC being an aggressive disease is that cancer cells disperse into the bloodstream of patients. Modern methods can detect these cells in peripheral blood. These “circulating tumor cells”, if successfully captured, can provide insight into the biology of this disease. This study analyzes the CTCs from two pairs of cell lines, NCI-H69/H69AR and MAR/MARV6. Each pair consists of the parental cell line and its drug-resistant counterpart. We performed a lyoplate biomarker screening assay to determine the variation in biomarker expression between the cell lines. We then used flow cytometry to validate the findings of the lyoplate assay for CD9, CD49b, CD56, and CD99 which have been postulated to be associated with drug-resistance. Although the biomarkers tested did not correlate with drug-resistance across cell lines, we identified biomarkers which were consistent and provide future opportunities for research.