Funded Research
An ESUN Announcement
February 15, 2010: The Liddy Shriver Sarcoma Initiative is pleased to announce the funding of a 1-year $50,000 research study, "Targeting the Tumor-Associated Antigen p27kip1 in Metastatic Osteosarcoma," that is being undertaken by principle investigator Tsz-Kwong Man, PhD in the Department of Pediatrics at Baylor College of Medicine in Houston, Texas.
The funding for this grant is made possible, in part, by generous donations made by family and friends in memory of Sammie Hartsfield (Team Sammie), in memory of Brandon Gordon (Brandon's Defense Foundation) and in memory of Emma Koertzen who lost their lives to osteosarcoma, and by generous donations made by the family and friends of Todd Andrews (Team Sarcoma Bike Tour), Logan Brasic (Soccer 'Round the Clock), and Shannon Ryan (Team Sarcoma Bike Tour) who are still fighting this disease or are survivors.
Baylor College of Medicine published an enlightening news release entitled, "Grant awarded to study protein involved in common bone cancer." Highlights of the story are included below:
HOUSTON -- (February 22, 2010) -- Dr. Tsz-Kwong Man, a researcher with the Texas Children's Cancer Center at Baylor College of Medicine, has received a grant from the Liddy Shriver Sarcoma Initiative to study the function of a protein that may promote the spread of a common form of children's bone cancer called osteosarcoma.
"This is a devastating cancer," said Man, principal investigator of the study. "Once the cancer spreads to other parts of the body, and it often does, it can be very aggressive and has poor survival rates."
That's why it is important to continue research into identifying a useful drug target to stop development of the cancer spread, Man said.
Using high-throughput technology, Man and his team look to identify panels of antibodies (proteins in blood that identify and kill foreign objects, such as bacteria and viruses) involved in metastasis – when the cancer spreads to other parts of the body.
Prior to receiving this grant, Man had identified an antibody targeting an important tumor-suppressing protein (p27kip1) that may help block a cell's path to cancer.
"This protein turns out to be very important in metastasis," said Man. "It may promote cell motility (ability to move spontaneously and actively) and formation of metastases."
The hypothesis, Man said, is that if this protein is mislocalized within the cytoplasm (contents of a cell, outside of the nucleus), it acquires a new cancer spreading function.
The Liddy Shriver Sarcoma Initiative grant, for $50,000 over one year, will allow Man to study the function of this protein along with other pathways involved in osteosarcoma.
The findings could lead to new therapies for osteosarcoma patients, Man said, and potentially other forms of cancer.
"We are delighted to be funding this research study by Dr. Man and hope that the results of his work lead to a better outcome for children with metastatic osteosarcoma and, potentially, other metastatic sarcomas as well," said Dr. Bruce D. Shriver, director of the research grants program at the Liddy Shriver Sarcoma Initiative.
Here is a summary of his research study:
Osteosarcoma is the most common bone cancer in children and adolescents, which accounts for approximately 60% of bone cancers in the first two decades of life. With the advent of chemotherapy, the survival rate of osteosarcoma patient has reached 60-70%. However, if the tumor cells metastasize to other parts of the body, the majority of affected patients will succumb to the disease. The major challenge of the field now is to develop a novel and targeted approach that can facilitate the treatment of patients with disease spread, allowing a more effective and personalized treatment to be given to those patients who are at risk. Previous studies have demonstrated that the body’s immunity generates specific autoantibodies, which target proteins that are important to the progression and malignancy of tumor cells. Using this autoantibody approach, we have recently identified tumor antigens that are specifically associated with the patients with metastatic osteosarcoma. The results of this study have shown that the autoantibody for the tumor suppressor protein p27kip1 was significantly higher in patients with metastatic osteosarcoma. Immunohistochemistry further indicated that the p27kip1 proteins were mislocalized in the cytoplasm of metastatic cells. These results are supported by recent reports that cytoplasmic sequestration of nuclear p27kip1 may promote metastasis in some cancers; however, its role in osteosarcoma is still elusive. Based on these findings, we hypothesize cytoplasmic mislocalization of p27kip1 promotes metastasis in osteosarcoma.
To test this hypothesis, we propose three specific aims. First specific aim: we will test if cytoplasmic location of p27kip1 is sufficient to promote metastasis in non-invasive osteosarcoma cells. Second specific aim: we will determine the phosphosite(s) in the p27kip1 protein that are important for p27kip1-mediated metastasis in the tumor cell. Third specific aim: we will conduct experiments to dissect the relationship of p27kip1 and the mTOR pathway, which has been previously implicated in metastasis of osteosarcoma. The long-term goal of this study is to improve the prognosis of osteosarcoma patients with metastasis. Elucidating the role of p27kip1 in metastatic osteosarcoma and its relationship with the mTOR pathway will enhance our understanding of the metastasis mechanism in osteosarcoma. Should the results of this proposed study be promising, we will further validate our findings using samples obtained from a large clinical trial study, such as EURAMOS. We will also test if p27kip1 could be used as a therapeutic target in metastatic osteosarcoma. Therefore, we believe that our proposed study will ultimately improve the dismal outcome of children with metastatic osteosarcoma and, potentially, other metastatic sarcomas as well.
You can learn more about this study in the article "Targeting the Tumor-Associated Antigen p27kip1 in Metastatic Osteosarcoma" this appears in the February 2010 issue of ESUN.
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