PDTB-15. Bcl-XL AS A RADIOSENSITIZER IN THE TREATMENT OF GROUP 3 MEDULLOBLASTOMA

Medulloblastoma is the most common malignant pediatric brain tumor. Although significant progress has been made in the treatment of medulloblastoma patients over the past several decades, the five-year disease-free survival for high-risk patients, characterized by metastatic dissemination at presentation or significant post-operative residual tumor, remains relatively poor (25-40%). Group 3 medulloblastoma has by far the worst prognosis with a 5-year survival probability of approximately 30% regardless of stage. Current therapeutic modalities, in particular ionizing radiation (IR), have significant long-term side-effects within the pediatric population. Enhancement of current therapies through targeted radiosensitization may allow for improved response and lead to decreased late radiation-induced sequelae. A bioinformatics approach was employed to select a number of candidate radioresistance genes that are preferentially expressed in group 3 medulloblastoma tumors. Candidate genes were tested for radiosensitization using RNA interference. Through this approach, we have identified and validated the antiapoptotic gene Bcl-XL as an effective target for the radiosensitization of medulloblastoma group 3 tumors. The siRNA results were confirmed with ABT-263, a small molecule inhibitor of Bcl-2 family members. ABT-263 potently radiosensitized D425MED group 3 cells with a dose enhancement factor (DEF) at 40% cell death of 2.2 and a concentration of 200 nM. As ABT-263 is not...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: PEDIATRIC TUMORS - PRECLINICAL STUDIES (NON-IMMUNOLOGICAL) Source Type: research