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Treatment of established, chemically induced non-small cell lung cancer with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)

English title Treatment of established, chemically induced non-small cell lung cancer with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
Applicant Frese Steffen
Number 118324
Funding scheme Project funding (Div. I-III)
Research institution Department for BioMedical Research Universität Bern
Institution of higher education University of Berne - BE
Main discipline Experimental Cancer Research
Start/End 01.10.2007 - 30.09.2008
Approved amount 54'508.00
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Keywords (5)

tumor necrosis factor-related apoptosis-inducing; ligand (Apo2L/TRAIL); receptor-mediated apoptosis; non-small cell lung cancer; NNK-induced lung cancer in A/J mice

Lay Summary (English)

Lead
Lay summary
Lung cancer is the leading cause of cancer death in the United States among both men and women. The projected number of new lung cancer cases in 2005 in the United States is 172’570, accounting for 13% of all new cancer cases and for 29% of all cancer deaths. In fact, more people die each year from lung cancer than from breast, colorectal, prostate, and ovarian malignancies combined. There is a similar situation in Europe with 375’000 new cases and 347’000 deaths related to lung cancer per year. Therefore, new treatment strategies are needed for this disease.A potential new treatment strategy for lung cancer might be the application of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL is a cytokine from the family of tumor necrosis factors which has been shown to induce apoptosis in vitro in cancer but not or much less in normal cells. In vivo, a number of groups demonstrated cytotoxic effects of TRAIL in experimental xenograft models using clonal cancer cell lines implanted in immunodeficient mice. The aim of our group was to evaluate the anti-cancer efficiency of TRAIL in a clinically more relevant model presented by chemically induced lung cancer in A/J mice. In addition we wanted to see whether these tumors might be sensitized to TRAIL-induced apoptosis by PG490 and CPT-11. Our results obtained in the last two years can be summarized as follows: 1. TRAIL alone using a dose of 500 mg but not a dose of 250 mg has some anti-tumor effects in our cancer model. 2. PG490 and CPT-11 were not able to sensitize to TRAIL-induced apoptosis in vivo. 3. Longer treatment of A/J mice with TRAIL leads to side effects most likely due to cross-species auto-antibodies of immunocompetent A/J mice against human TRAIL. Based on these results we plan to perform the following experiments: Repetition of the shorter treatment schedule in A/J mice using 500 mg TRAIL in order to acquire a substantiated statistics of tumor number and volume from TRAIL treated mice compared to control mice. After sacrificing A/J mice tumors will be implanted in immunodeficient NOD-SCID mice and further treated with TRAIL. Treatment of A/J derived lung tumors in NOD-SCID with TRAIL is planned to prevent undesirable side effects of cross-species antibodies. Applying this protocol we hope to clarify the important question whether TRAIL might have anti-tumor activity against established lung cancer.
Direct link to Lay Summary Last update: 21.02.2013

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