Development of novel small molecules against cancer stem cells in solid cancers
Grant Award Details
Grant Type:
Grant Number:
DISC2-14083
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$2,340,000
Status:
Active
Grant Application Details
Application Title:
Development of novel small molecules against cancer stem cells in solid cancers
Public Abstract:
Research Objective
To study and optimize lead compounds with multi-kinase activity against existing glioma stem cells and radiation-induced phenotype conversion of non-stem glioma cells into induced glioma stem cells.
Impact
Glioblastoma is a universally deadly disease. While radiotherapy prolongs survival in glioblastoma it has hit a critical barrier. The proposed study aims to improve the efficacy of radiotherapy in GBM
Major Proposed Activities
To study and optimize lead compounds with multi-kinase activity against existing glioma stem cells and radiation-induced phenotype conversion of non-stem glioma cells into induced glioma stem cells.
Impact
Glioblastoma is a universally deadly disease. While radiotherapy prolongs survival in glioblastoma it has hit a critical barrier. The proposed study aims to improve the efficacy of radiotherapy in GBM
Major Proposed Activities
- Define and validate the molecular targets of MXC017 and MXC079 in vitro and in vivo
- Optimize the MXC017 and MXC079 to increase their activity against existing glioma stem cells and to prevent radiation-induced conversion of non-stem glioma cells into induced glioma stem cells
- Perform PK studies in tumor-bearing mice
- To demonstrate efficacy of MXC017 and/or MXC079 against glioblastoma alone and in combination with radiation in patient-derived orthotopic models of glioblastoma
Statement of Benefit to California:
Glioblastoma is a universally deadly disease and treatment outcome has not been improved for two decades.
The standard-of-care for patients with glioblastoma is surgery, followed by radiotherapy and chemotherapy and the median survival is only 15-18 months. The proposed studies aim to develop novel compounds against glioblastoma that will enhance the efficacy of radiotherapy to improve survival for patients with GBM, thereby improving value-based care and the life of Californians.