Research Grants

2003 SFA Research Grant Recipients

Targeting the Inactivation of the MYC Oncogene to Treat Osteogenic Sarcoma

• Dean Felsher, M.D., Ph.D. Stanford School of Medicine Stanford University Medical Center Stanford, California
• Recipient of a $25,000 research award
• Abstract: We have found that even brief inactivation of the MYC oncogene can result in sustained regression of osteogenic sarcoma (Jain et al, Science, 2002; Weinstein, Science, 2002). Now, we propose to perform several pre-clinical studies to evaluate the effectiveness of a novel anti-sense approach for the inactivation of MYC for the treatment of osteogenic sarcoma. We will evaluate the mechanisms by which brief inactivation of MYC induces tumor regression through cDNA microarrrays. From these experiments, we will obtain the preliminary results necessary to subsequently conduct a clinical trial to evaluate the effectiveness of the inactivation of MYC to treat human osteogenic sarcoma.
• Final Report: Our lab had previously shown if you transiently shut down a cancer gene, called MYC, that this causes osteogenic sarcoma tumors to lose their neoplastic properties - that is, the tumor regresses. As a result of this grant, we have developed a new way to shut off MYC using a synthetic RNA. We have shown that this agent shuts off the cancer properties of osteogenic sarcoma cells in tissue culture. We are evaluating if this approach can be used to suppress cancer cells in a living host such as the mouse. The results of my work will be useful towards the development of new treatments for osteogenic sarcoma patients.

Generating T cell Immunity to Sarcoma by Liposomal Vaccination with Sarcoma Fusion Breakpoints

• Mary Jo Turk, Ph.D. and Jose A. Guevara-Patino, M.D., Ph.D. Memorial Sloan Kettering Cancer Center; New York, NY
• Recipient of a $25,000 research award
• Abstract: We have developed a liposomal vaccine that delivers long peptides into the processing/presentation machinery of antigen presenting cells and generates outstanding cytotoxic T cell responses. We propose the use of this vaccine for generating T cell immunity to the breakpoint regions of four sarcoma-derived oncofusion proteins: EWS-ATF1, SYT-SSX, TLS-CHOP, and ASPL-TFE3. Experiments will be conducted to demonstrate that peptides within these breakpoints 1) are processed and presented by human antigen presenting cells, and 2) activate a population of cytotoxic T lymphocytes capable of killing human sarcoma cells. These studies will facilitate rapid clinical translation of four novel sarcoma vaccines.
• Final Report: This project was aimed at validating vaccines against four oncofusion proteins (expressed when an oncogene, such as EWS, integrates into or fuses to another gene, such as ATF1) produced by sarcomas. We injected these proteins and studied the immune reaction to see if this type of vaccine could elicit an immune response. Based upon our results, we can conclude that the human immune system does contain T cells that can potentially react against the breakpoint regions (which produce the oncofusion proteins) of these sarcoma-specific proteins. This is encouraging because these reactive T cells could potentially kill sarcoma cells containing the oncofusion proteins, and it was originally thought that there were very few T cells (1 in 100-500,000) that can recognize these antigens. We have also optimized a vaccine delivery system based on use of liposomes (microscopic spheres made with fat molecules), which will be used in conjunction with these sarcoma antigens to provide maximum T cell responses against sarcomas clinically. We believe that the results obtained in this study, in conjunction with future studies, will facilitate the development of vaccines directed against sarcoma breakpoints that can be used in sarcoma cancer patients.

Identification of Tumor Suppressor (LOH18CR) on Chromosome 18

• Antony E. Shrimpton, Ph.D. and Timothy A. Damron, M.D. State University of New York, Upstate Medical University; Syracuse, NY
• Recipient of a $20,000 research award
• Abstract: We have identified and studied a family with familial Paget’s disease of bone and Pagetoid osteosarcoma. A familial pattern is extremely unusual and indicates the presence of a putative germline mutation in a tumor suppressor gene involved in osteosarcoma. We have demonstrated loss of heterozygosity for markers located on the long arm of chromosome 18q which includes a 530 kb critical region defined by others, which is believed to contain an osteosarcoma tumor suppressor gene. We wish to sequence candidate genes, in close to this region or otherwise implicated, in order to identify a pathogenic mutation, and thus the tumor suppressor gene.
• Final Report: In our previous studies, we had identified a family with an inherited disease of bone and a rare type of bone cancer (osteosarcoma). For this to be inherited is extremely unusual and probably indicates the presence of a mutation in a gene involved in bone cancer in this family. Our studies led us to suspect that a small fragment of chromosome 18 probably has a mutation in a gene important in preventing this type of bone cancer from developing. Thus, we wanted to search for this osteosarcoma suppressor gene by testing for candidate genes on this chromosome (known to be abnormal). As a result of the grant, we have now tested twelve candidate genes. Unfortunately, we did not yet find a mutation, so as proposed, we will now test another two candidate genes from this chromosome and then two other genes known to have similar effects, but located in other chromosomes. While the search for a key mutated gene for osteosarcoma continues, we have narrowed the search by eliminating all of the above genes.

Programs & Resources

Information on sarcoma subtypes, treatments, clinical trials, and other important resources for sarcoma patients and families.

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Information on applying for a sarcoma research grant, current research funded by the SFA, and past research grants.