Dr.Morris Poster for Preclinincal research released for WLCC
Session Info: Poster Session, [P2] Poster Session 2
Day/Date: Tuesday, July 5, 2011
Session Time: 12:15 PM - 2:00 PM
Room: Exhibition Hall
P2.033 | Evidence of Significant Efficacy of the Oncolytic Virus, Reovirus, for the Treatment of Lung Cancer
A. Kellar, N. Ronaghan*, Z.Q. Shi, C. Thirukkumaran, D. Morris
University of Calgary/CANADA
Background:
Lung cancer is the leading cause of cancer mortality worldwide. It is estimated that approximately 1,529,560 people were diagnosed with cancer in 2010, resulting in approximately 569,490 deaths. Surgical resection and aggressive chemotherapies prove to be only marginally effective as five-year survival ranges from 13% in men and 17% in women. Reovirus (RV), a double-stranded RNA virus, has been shown to be effective against a myriad of cancers through its ability to preferentially lyse cancer cells with aberrant Ras or other pathway signaling. In this study, we investigate the potential of RV (serotype 3, strain Dearing) as a novel treatment for both non-small cell and small-cell lung cancer in vitro and in vivo.
Methods:
RV-induced cytotoxicity was assessed by WST-1 viability assays for both NSCLC cell lines: (A549, H460, H1299, HCC4006, H1975, H226, HCC827, HCC2935) and SCLC cell lines: (DMS-53, and H69) in vitro. RV and chemotherapy combination studies were conducted for the DMS-53, H69, HCC827 and H226 cell lines, evaluating the cytotoxic effects of reovirus in combination with each of the following: cisplatin, pemetrexed, etoposide, and erlotinib using the constant-ratio design and combination index method of Chou Talalay. In order to further evaluate the potential of RV as novel therapeutic for lung cancer, three xenograft models (H460, H1299 and DMS-53) were utilized to test RV-induced cytotoxicity alone and in combination with chemotherapy in vivo.
Results:
RV induces cytotoxic effects at a multiplicity of infection (MOI) of 40 within 48h for both NSCLC cell lines: (A549, H460, H1299, HCC4006, H1975, H226, HCC827, HCC2935) and SCLC cell lines: (DMS-53, and H69) in vitro. These findings are particularly unique for SCLC, in that effective therapies are limited. Interestingly, preliminary data also suggests that RV in combination with chemotherapy has potentially synergistic cytotoxic effects in vitro. In addition, current xenograft data indicates that both the H460 and H1299 cell lines are intrinsically sensitive to RV in vivo. Updated results will be presented.
Conclusion:
These preclinical results suggest that RV holds promise as a novel therapeutic for both non-small cell and small cell lung cancer and that it warrants further investigation in clinical trials. There is currently a phase III (Typo should be Phase II) clinical trial for RV in combination with carboplatin for the treatment of NSCLC. These results may suggest that other combinations should be examined and that RV may have the potential to revolutionize therapy for SCLC.
