An international and cross disciplinary set of nine new projects will go forward thanks to grants from MARF of $100,000 each. Researchers in Holland, Australia and the United States combined their efforts to field a broad spectrum of investigative efforts that are certain to advance the pace and scope of research success against this deadly cancer. Meso is a malignant tumor related to asbestos exposure that aggressively invades the mesothelial linings of the lungs, abdomen, heart or testicles.
MARF's scientific experts selected the nine projects as the most important and promising among 28 high caliber applications received from around the world. For each of these two-year projects, the researchers are bound by strict budgeting and progress reporting requirements. Funds for the first year were paid in late 2005 and the research is now underway.
In a Phase I clinical trial focused on immune therapy, Doctor B.N.M. Lambrecht of the Erasmus Medical Center in Rotterdam, the Netherlands, plans to evaluate dendritic cells as a therapeutic adjuvant for treating malignant meso in humans. This grant follows up on previous successes with immunotherapy studies in mice that were very effective and also funded by MARF. Dendritic cells proved capable of generating an immune response when presenting meso tumor antigens and the current study intends to test the feasibility and safety of this approach.
Hot on the heels of meso-specific serum biomarker announcements in late 2004 and early 2005, researchers at USC under the direction of Dr. Ite Laird-Offringa were given a grant to continue investigating diagnostic markers for meso. USC plans to use DNA microarray chips to pre-screen 6500 serum markers using the MethyLight analytical system. Tissue samples would be examined to identify specific molecular markers found in meso tumor specimens with an eye to developing new serum tests to aid early diagnosis of the cancer.
The molecular understanding of the human genome has allowed researchers to undertake much more precise and tactical interventions against meso. Professor Xiaobo Cao of Texas A&M University, and his team, received a grant to investigate a specific gene family bcl-2, known to over-express a protein BCL-XL which blocks cell death (apoptosis) in mesothelioma tumors. Researchers wish to evaluate a bcl-2/bcl-xl antagonist, a compound that blocks the actions of the over-expressed protein, to see if it will cause tumor cell death and sensitize meso cells to the effects of existing chemotherapy agents. Such studies were virtually impossible ten years ago and represent the leading edge of scientific research today.
A Nevada Cancer Institute team under the direction of Dr. Sunil Sharma will continue its investigation of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor. SAHA and other HDLC inhibitors have demonstrated broad cancer activity and provide a promising new approach to therapy. Tumor resistance to HDAC inhibitors will be studied in an effort to identify combination therapies with mTOR inhibitors and nutrient uptake inhibitors that can increase tumor response to treatment. Dr. Sharma intends to generate a meso cell line resistant to SAHA and other drugs like valproic acid and then compare them to parent cell lines using molecular analysis to identify markers of resistance. These markers will then become targets for therapy.
MARF funded five other, equally innovative and important studies in this latest round of grants. Some of these research grants will become stepping stones; used to provide sufficient data to propose and win larger research grants from the National Institute of Health (NIH) and other government agencies. Using this approach, MARF-funded projects have had a multiplier effect on the total research investment into a cure for mesothelioma. Taken together, these studies have achieved, and will continue to achieve, results far in excess of what MARF could have accomplished alone. Without MARF's investment, however, little progress would have taken place.
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