Funded Research:
Targeting bone microenvironment as a new therapeutic strategy in Ewing’s sarcoma
June 15, 2011: The Liddy Shriver Sarcoma Initiative is pleased to announce the funding of a $90,000 research grant, "Targeting bone microenvironment as anew therapeutic strategy in Ewing’s sarcoma: combination of zoledronic acid with chemotherapy in mouse preclinical models." This study is being conducted by co-principal investigators Françoise Rédini, PhD, Research INSERM Director, Medicine Faculty, Nantes, France and Nadège Corradini, MD, Pediatric Oncologist, Mother & Child Hospital, Nantes, France.
This grant is made possible by very generous gifts from the Arlo and Susan Ellison Family, the Jack Langseder 4evRSTRONG Foundation and Strike Out Sarcoma (in memory of Michael Lio).
In their grant application, Drs. Redini and Corradini note that:
"Ewing’s sarcoma (EWS) represents the second cause of malignant bone tumors in children and adolescents, with a peak incidence at 15 years old. In Europe, most patients are treated in the Euro-EWING99 clinical trial, with 73% event-free survival (EFS) at 3 years for localized tumors. Survival rates are poor, however, for patients with metastases outside the lungs or pleura and patients not responding to chemotherapy (EFS and overall survival < 30%). Therefore, there is an urgent need to develop adjuvant therapies to improve the outcome of these patients."
Drs. Redini and Corradini go on to state:
"Tumor development in bones is associated with the existence of a vicious cycle between tumor cell proliferation and bone resorption. Therefore, targeting the bone resorption process represents an interesting therapeutic option for these tumors. The present project aims at combining zoledronic acid, a potent inhibitor of bone resorption, with chemotherapy in preclinical models of Ewing's sarcoma.
"The objectives of this program are therefore to study the potential therapeutic effects of zoledronate (ZOL) alone or combined with chemotherapy in Ewing's sarcoma using complementary in vitro analyses (mechanisms of action: proliferation, apoptosis, cell cycle, resistance) and preclinical approaches (bone and soft tissue models of primary Ewing's sarcoma induced by injection of human tumor cells respectively in the tibia medullar cavity or in an intra-muscular site in immune-deficient mice). The effects of this therapeutic combination will also be studied in models of bone or pulmonary metastases induced by injection of Ewing's sarcoma cells via intraveinous or intracardiac routes, respectively. Indeed, the patients with high risk of relapse are those who present with metastases at diagnosis or whose tumors are resistant to chemotherapy."
Dr. Redini stated, "The impact of these studies will be to propose zoledronic acid as adjuvant therapy for Ewing's sarcoma patients in the next European protocol (following the current EuroEWING99) to help prevent recurrence and metastasis and to improve prognosis for patients with metastatic or unresponsive disease."
Read more about this study in the article, "Targeting Bone Microenvironment as a New Therapeutic Strategy in Ewing’s Sarcoma: Combination of Zoledronic Acid with Chemotherapy in Mouse Preclinical Models," which appears in the June 2011 issue of ESUN.