Development of Novel Therapy for Glioblastoma Targeting Therapy-Resistant Cell Population by Modulation of DNA Repair and Immune Response
Abstract
Glioblastoma (GBM) is a rare cancer, with an annual occurrence rate of 3.22 per 100,000 persons. Although rare, GBM is a very aggressive type of brain cancer with a miserable outcome upon diagnosis. Currently, surgical resection, followed by radiotherapy with concomitant chemotherapy with temozolomide is the standard of care for the disease. However, resistance to radiation and chemotherapy is the biggest challenge in the treatment of GBM patients. A small group of cells known as glioblastoma stem cells (GSC) is responsible for therapy resistance. It is a well-known strategy that killing cancer stem cells can improve the chemotherapeutic effect by reversing chemotherapy resistance and preventing cancer recurrence. Radio- and chemoresistance in GSCs depends on the mechanism that repairs DNA double-strand breaks. Thus, blocking DNA repair is an effective strategy to kill GSCs. DNA repair is performed by DNA repair protein RAD51, thus blocking of RAD51 activity by RAD51inhibitors may improve the effectiveness of chemo- and radiotherapy. Moreover, GBM treated with RAD51inhibitors may modulate neoantigen production and thus, may be useful for immunotherapy. We hope that blocking the function of RAD51 protein using small molecules will kill GSCs and improve the effectiveness of radiotherapy and chemotherapy, which in turn improve the overall survival of GBM patients. The proposal is focused to test the unique therapeutic strategy to treat the rare cancer glioblastoma. Successful completion of the project will open a new avenue in the field of immunotherapy research for this type of rare cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210699
Entities
People
- Soma Samanta
Organizations
- United States Army
- University of Michigan