Abstract C106: Screening small cell lung cancer lines against approved oncology drugs and investigational agents elucidates patterns of sensitivity.
Authors: Evans David M. , Delosh Rene , Laudeman Julie , Ogle Chad , Reinhart Russell , Selby Michael , Silvers Thomas , Monks Anne , Kaur Gurmeet , Morris Joel , Teicher Beverly A. 
Published: August 2014

Small cell lung cancer (SCLC) is an aggressive cancer with a 5-year survival rate of &lt;5% that frequently recurs after conventional cytotoxic chemotherapy. We have undertaken a systematic large-scale screening of approved oncology drugs and investigational agents for activity against SCLC in an effort to provide new leads to effective treatment of this disease. Our laboratory compiled a panel of &gt;75 human SCLC lines and is screening approximately 60 (well characterized) lines against 103 agents from the Approved Oncology Drugs (AOD) library) and 420 agents from the Investigational Agents library. Compounds are evaluated at 9 concentrations (10uM to 1.5nM) in comparison with vehicle controls using cell viability 96h post drug exposure as the endpoint - allowing a direct comparison between the IC50, anticipated compound molecular target and the breadth of activity across the cell lines. These cells represent a broad coverage of those available as representatives of SCLC with an array of growth behaviors. Cell lines grow as adherent cultures, in single cell suspension, in suspension as spheres and /or clumps, or mixed cultures. Despite these varied phenotypes, the screen was robust (Z’ score &gt; 0.5) in all of the lines studied to date. Interestingly, SHP77 (an unusual undifferentiated large cell morphological variant with biochemical properties of SCLC) consistently showed lower sensitivity to the drugs than other cell lines tested. Trends emerging from the early data indicate that: 1) Comparing compound activity (IC50 value) by cell line and clustering the compounds based on their reported targets, we could readily observe the target classes that produced the greatest cell growth inhibition across the widest set of the SCLC cell lines; and 2) from these data it appears that discrete HDAC inhibitors and HSP90 inhibitors produce potent growth inhibition across a wide array of SCLC lines (including SHP77). We are expanding the number of SCLC lines under study. Each cell line will be examined for gene expression patterns, miRNA expression patterns and sensitivity to the approved and investigational agents (IC50). These data will allow correlations to be made regarding sensitivity of the cells to agents with discrete cellular targets versus the genomic background in these cells. Data from the drug screens combined with genomic profiling of the cells may allow clinical trials to select therapeutic agents to maximize benefit in patients presenting with SCLC. Further analyses and findings from the data will be presented.

Funded by NCI Contract No. HHSN261200800001E.

Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C106.

Citation Format: David M. Evans, Rene Delosh, Julie Laudeman, Chad Ogle, Russell Reinhart, Michael Selby, Thomas Silvers, Anne Monks, Gurmeet Kaur, Joel Morris, Beverly A. Teicher. Screening small cell lung cancer lines against approved oncology drugs and investigational agents elucidates patterns of sensitivity. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C106.