Foundation awards $500,000 for mesothelioma research projects
Research projects at Memorial Sloan-Kettering Cancer Center, the University of Pennsylvania and Brigham and Women’s Hospital are among five initiatives that will split $500,000 in grants from the Mesothelioma Applied Research Foundation.
The five projects, chosen by mesothelioma experts on the foundation’s Science Advisory Board, are aimed at developing new treatments for the deadly disease, a rare cancer caused by asbestos exposure. Mesothelioma kills about 3,000 Americans each year and has no known cure and limited treatment options.
The projects funded this year include a study that will combine genomic data on pleural mesothelioma tumors in an attempt to define how defective genes impact cells that become malignant. Another study, conducted at the University of Pennsylvania, will investigate how interferon gamma — a protein in the immune system — regulates the response of tumor cells to the mesothelioma drug Pemetrexed.
Kathy Wiedemer, the foundation’s executive director, said the nonprofit’s peer-review process has identified projects that could make significant contributions to the understanding and treatment of mesothelioma.
“This year we have awarded another half million dollars toward the search for a cure,” Wiedemer said. “Our mission to cure meso is clear and we won’t stop until it’s accomplished.”
The Mesothelioma Applied Research Foundation’s grant program has awarded more than $7.5 million since 2000. In addition to funding new research, the organization provides patients with information on treatment options and lobbies for greater federal involvement in mesothelioma research.
The 2011/2012 grant winners are:
Tao Dao, Memorial Sloan Kettering Cancer Center: WT1 has become an attractive target in mesothelioma. Antibody therapy is a way to target proteins but WT1 is not expressed on the outside of the cell thus making the use of monoclonal antibodies an effective way in which to target WT1. To target WT1 using an immunological approach this proposal will use peptides that are presented by HLA-A2 molecules (human leukocyte antigen A-2 which are antigens that help the immune system detect foreign invaders) as a carrier to target and kill mesothelioma cells.
Assunta DeRienz, Brigham and Women's Hospital: This project aims to explore the whole-genome data of ten MPM tumors and matched normal for the identification of both therapeutic targets in individual genes, specific pathways and predictive biomarkers. Novel molecular mechanisms will be revealed. This proposal will attempt to combine all genomic data to obtain insight to the molecular mechanism of MPM, by identifying recurrent mutated genes, associating them to defective pathways, and defining different subgroups of MPM patients.
Marc Ladanyi, Memorial Sloan-Kettering: Dr. Ladanyi and his group analyzed the genome of 53 malignant mesothelioma tumors and have reported that BAP1 inactivation or loss occurs in approximately 42% of mesotheliomas. The role of BAP1 in malignant mesothelioma has yet to be clarified and may prove to be of interest in both the pathogenesis of mesothelioma, cell proliferation or even cell death. The proposal will look at three sets of experiments to characterize how the loss of BAP1 may cause
mesothelioma to become more vulnerable to either existing or novel targeted therapy approaches.
Liang-Chuan S Wang, Perelman School of Medicine at the University of Pennsylvania: This project will investigate how the IFN (interferon-gamma, an important protein in our immune system) pathway is involved in regulating the response of mesothelioma cells to chemotherapy-induced cell death. A better understanding of this protective mechanism can further assist in determining optimal treatment strategies and potentially augmenting effects of chemotherapy. Despite numerous new chemotherapeutic agents being developed over the last two decades, the median survival after receiving these drugs remains around 12-15 months. Recently, our group has found a protective mechanism used by mesothelioma cells to resist chemotherapy. If we understand and harness this properly, it may be possible to optimize the current treatment strategy to improve clinical outcomes.
Nadia Zaffaroni, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy: The main aims of the project are: i) the identification of dysregulated miRNAs in Diffuse Malignant peritoneal mesothelioma (DMPM) to discover specific miRNAs acting as key players in disease incidence and progression. In addition, through the prediction and validation of the targets of such miRNAs, we propose to shed light on the biological mechanisms and regulatory events through which they lead to mesothelial carcinogenesis (changing cells from benign to malignant); ii) the identification of up-regulated miRNAs in blood of DMPM patients, which could represent new biomarkers for monitoring DMPM patients following treatment and, possibly, anticipating the clinical diagnosis of recurrence (similar to prostate where we follow PSA); iii) the identification of miRNAs significantly associated to patient prognosis, which could be used in combination with conventional clinico-pathological variables for the selection of patients who will benefit from this specific treatment (helping to understand who best benefits from a particular therapy) iv) the functional validation of specific miRNAs as possible novel therapeutic targets or tools in DMPM, through the analysis of the consequences of modulation of their expression on the phenotype of human DMPM experimental models in vitro and in vivo (both cell and animal models).