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2010 Mesothelioma Research Grant Awards

Chuong Hoang, MD
Stanford University

Title: Mesothelioma Biomarker Development Drive by microRNA-mRNA Regulatory Module Network Analysis

Description: The work proposed will break the current paradigm of assuming that there is one critical biological pathway/molecule that determines development of mesothelioma. The propsal hypothesizes that the interactions and communications between certain biological pathways and/or genetic molecules influence development of mesothelioma. The goal is to characterize and understand the interconnectedness of these active biological pathways and/or geneticism molecules in mesothelioma. In doing so, this will help to develop better biomarkers.


Fengzhi Li, PhD
Roswell Park Cancer Institute

Title: Validation of a novel antiapoptotic protein inhibitor for mesothelioma treatment

Description: Dr. Li has discovered a novel compound called FL118 that inhibits multiple anti-apoptotic proteins (apoptotic is programmed cell death which is the way we eliminate damaged cells) and BCL proteins (which are associated with chemotherapy resistance). He has tested this compound in head and neck cancer, and colon cancer. The results have been very promising in animal models of these two malignancies. FL118 will be injected into mice in which mesothelioma has been implanted to directly observe the effect of this compound in an animal model for both toxicity and response. If this experiment is positive it will be available to move into human studies quickly. 


Bin Liu, PhD - Lance S. Ruble & Ferraro Law Firm Grant
University of California at San Francisco

Title: Internalizing scFv-targeted intracellular delivery of small RNA therapeutics to all subtypes of mesothelioma

Description: The goal of this proposal is to develop effective small interfering RNA (siRNA) therapeutics against mesothelioma. siRNA silences the expression of the specified genes and thereby can be used to target specific pathways and cause cell death. The problem is that siRNA is not normally taken up into mammalian cells. Through initial funding by the Foundation, Dr. Liu identified a panel of internalizing human antibodies that target both epithelial and sarcomatous mesothelioma cells. This was done using a library of antibodies and testing them against mesothelioma cell lines. He now plans to combine these antibodies with the siRNA as a vehicle to deliver the siRNA directly into the cell. The efficacy of the various antibodies will be assessed in cell lines, and then the most promising ones will be further tested in a mouse xenograft model.


Jill Ohar, MD - Franz Losch Memorial Grant
Wake Forest University School of Medicine

Title: Consortium for the sharing of germ line DNA and tissue from subjects with mesothelioma

Description: Genetic variation, in addition to asbestos exposure and host factors, contribute to the development of mesothelioma. Because of the scarcity of mesothelioma and the large number of samples required for genetic analysis, no one center can possibly accumulate sufficient numbers of samples from subjects with mesothelioma to adequately evaluate genetic risk. Therefore, it is the aim of this proposal to develop a consortium of mesothelioma investigators to share DNA samples. The goal is to collect 1000 DNA samples from patients with mesothelioma and use these samples to perform genome wide association scanning (GWAS). This will help identify genetic risk factors for developing mesothelioma. 


Manish R. Patel, DO - Beth Ann Miller Memorial Grant
University of Minnesota

Title: Evaluation of predictive biomarkers and the host immune response to intrapleural administration of oncolytic Measles virus in a phase I clinical trial specifically for patients with mesothelioma

Description: The University of Minnesota is conducting a Phase I study of an oncolytic measles virus that will be delivered directly into the pleural space. Oncolytic viruses work by selectively infecting tumor cells, multiplying within the cell in their usual fashion, and thereby causing the cell to die. This proposal aims to evaluate potential biomarkers that will predict a response to measles virus therapy given to patients with mesothelioma on this phase I clinical trial. They also plan to characterize the immune response in patients treated with the virus to determine if this treatment will result in an antitumor immune response.


Yolanda L. Colson, MD, PhD
Brigham and Women’s Hospital

Title: Tumor-Localizing Polymeric Nanoparticle Drug Delivery for the Treatment of Malignant Mesothelioma

Description: Nanoparticles are solid particles, much smaller in size than a single cell, that have been proposed as a new approach to deliver chemotherapy directly to cancer cells left behind after surgery. “Chemotherapy-releasing” nanoparticles enter the tumor cells where changes in the cellular environment cause the nanoparticle to swell and release the chemotherapy inside the cell. Treatment with these nanoparticles in the operating room after removing the tumor may allow targeted delivery of chemotherapy directly to tumor cells remaining in the chest and/or abdomen following surgery. This project aims to assure that nanoparticles 1) are capable of efficiently killing malignant pleural mesothelioma cells in culture, and 2) prevent recurrence of malignant mesothelioma in a mouse model after surgery.


Sheelu Varghese, PhD
University of Maryland School of Medicine

Title: Pre-Clinical Development of a Novel Therapy for Malignant Peritoneal Mesothelioma

Description: The PI3K and mTOR signaling pathways regulate important cellular functions like growth, division, and survival. Preliminary studies from this investigator show high expression of these genes in peritoneal mesothelioma tumor samples, and that high expression was associated with aggressive tumor behavior and poor patient survival. This project will explore the therapeutic value of inhibiting P13K and mTOR signaling pathways. It is anticipated that if positive, it can move quickly into the clinic as there are currently a number of agents being explored in other cancers.