The RIS Board authorized $105,000 at its February 2014 Board meeting for 3 new sarcoma research projects through the U of M Masonic Cancer Center and three RIS Sarcoma Cancer Fellowships for the 2014-2015 Academic year. These awards are the direct result of the broad and deep support that RIS received in 2013. We thank you.
The awarded research grants for 2014 are:
$40,000 Grant Award: “Targeting Semaphorin-4D for Osteosarcoma Therapy”
Principal Investigator: David A. Largaespada, Ph.D. Collaborators: Dr. Branden Moriarity, Ph.D., Department of Pediatrics, University of Minnesota
This research is aimed at testing a new therapy to treat osteosarcoma (OS), which could be used in patients who have OS that has spread to the lungs and that is not responding to chemotherapy. At present, no effective therapy is available for these patients. Our new therapy will be tested in OS cells in tissue culture dishes and in mice in which human OS cells are growing. This new therapy is based on new genetic data that the Largaespada lab has generated showing that 2 cell surface proteins called SEMA4D and SEMA6D drive the growth and development of OS. As these proteins are on the surface of OS cells we think that antibodies that bind to SEMA4D and SEMA6D could effectively kill OS cells by a variety of mechanisms. No antibody-based therapy is part of OS treatment at the present time, but several other types of cancer are effectively treated in this way, including some breast cancers. Humanized or fully human antibodies that bind to SEMA4D are available from a company called Vaccinex and other sources, and these can be used in human patients as a drug. This research, if successful, will be followed by a phase I clinical trial in human OS patients to determine if it is effective.
Osteosarcoma is the most common primary bone malignancy affecting children, adolescents and young adults. Despite combined treatments, over 30% of patients with localized osteosarcoma and 70% of patients with metastasis at presentation experience treatment failure within five years of diagnosis. This dismal outcome has remained static for 20 years and the current standard-of-care chemotherapy has serious and potentially long-term side effects. There is an urgent need to improve overall survival and minimize long-term side effects. We have found a unifying feature of osteosarcoma is the overexpression of miR-17-92 microRNAs, and our preliminary studies show that osteosarcoma is oncogenically addicted to miR-17-92 expression that likely worsens clinical outcomes. We will investigate miR-17-92 as a potential therapeutic target in osteosarcoma, which will critically advance our understanding of osteosarcoma progression and will lay the foundation for improving overall survival in patients with osteosarcoma.
$30,000 Grant Award “Correlation of Macrophage Infiltration and Microvessel Density to Clinical Outcome in Sarcoma Patients”
Amy P.N. Skubitz, Ph.D., Professor Academic Dept: Laboratory Medicine and Pathology
Soft tissue sarcomas encompass a diverse group of malignant tumors that can spread to other sites of the body or can reappear at the site of the original tumor following surgery. In several types of cancer, researchers have studied the tissue surrounding cancer cells with the goal of identifying proteins or other types of cells that may alter the cancer cells, causing them to be more aggressive and metastatic. In some types of cancer, researchers have identified a protein that cancer cells secrete, called macrophage colony stimulating factor-1 (CSF-1). This protein attracts macrophages, a type of white blood cell, to the cancer cells in the tumor. Over time, the cancer cells are able to promote the development of new blood vessels to the tumor, so that the tumor will have the nutrients essential for further growth. In this study, we propose to examine a set of 70 sarcomas that we have accrued from a clinical trial for the presence of markers for CSF-1, macrophages, and blood vessels. We will determine whether there is a correlation between the clinical outcome of our patients and the presence of these markers, which may serve as targets for new therapies.
With the 2014 grant awards, Rein in Sarcoma funded over $1.1 million in grants for sarcoma research that has in turn levereged over an additional $4.5 million in additional sarcoma research at the University of Minnesota. All of this work is possible because of hundreds of committed and generous donors.
For Listing of previous RIS Research Grants, click here.