Research Breakthroughs Made Possible With Olivia Caldwell Foundation Grant Funding
The Olivia Caldwell Foundation has provided more than half a million dollars in support of pediatric cancer research over the past 7 years. Our research team has leveraged that money incredibly well, which has led to multiple breakthroughs that have drastically changed the way pediatric brain cancer is treated (and in some cases) has led to the cure for previously unsurvivable childhood cancers. The research breakthroughs attributed to the funding provided by the Olivia Caldwell Foundation include:
#1 - The Development of Targeted Therapy For Low Grade Gliomas:
One of the biggest breakthroughs our research team has had in the past 7 years with OCF funding has been the movement away from traditional IV chemotherapy to targeted oral therapy in low grade gliomas, which are the most common tumors in childhood. They have used this knowledge to effectively treat:
#2 - The Development of Therapy to Overcome Resistance to Targeted Therapy:
In some cases a child is able to successfully enter remission from a Low Grade Glioma using targeted therapy only to have that tumor recur some time later. When this happens the tumor can become resistant to the previously used targeted therapy, making it incredibly difficult to treat again. Our research team discovered that by adding an autophagy inhibitor to the previously used targeted therapy they can make the tumor sensitive to the targeted therapy again, thus leading to vastly better survival rates. They have used this knowledge to effectively treat:
#3 - The Development of Targeted Therapy for High Grade Glioma (HGG):
It was first assumed that targeted therapy would be of limited use in HGG given that these very aggressive tumors often have more than one driver However, in certain types of HGG we have shown using targeted therapies (often combined with the anti-autophagy therapy) was a successful approach. Typically children with these tumors would have passed within 6 months. These children are now surviving thanks to the development of targeted therapy (+/- autophagy therapy) thanks to OCF. They have used this knowledge to effectively treat:
#4 - Exploration of all the Cells in a Low Grade Glioma Using Single Cell Deep Sequencing Techniques (ongoing):
Our research team can now use new sequencing techniques to look at the entire DNA of a single cell. By looking at this for 1000s of cells in a tumor they can obtain an in-depth look at not only what each cell in a tumor is but what each cell is programmed to do. This sequencing has enabled the team to:
#1 - The Development of Targeted Therapy For Low Grade Gliomas:
One of the biggest breakthroughs our research team has had in the past 7 years with OCF funding has been the movement away from traditional IV chemotherapy to targeted oral therapy in low grade gliomas, which are the most common tumors in childhood. They have used this knowledge to effectively treat:
- Braf Driven Tumors
- FGFR1 and FGFR3 Driven Tumors
- NF Driven Tumors
- NTRK Driven Tumors
#2 - The Development of Therapy to Overcome Resistance to Targeted Therapy:
In some cases a child is able to successfully enter remission from a Low Grade Glioma using targeted therapy only to have that tumor recur some time later. When this happens the tumor can become resistant to the previously used targeted therapy, making it incredibly difficult to treat again. Our research team discovered that by adding an autophagy inhibitor to the previously used targeted therapy they can make the tumor sensitive to the targeted therapy again, thus leading to vastly better survival rates. They have used this knowledge to effectively treat:
- Resistant Braf Driven Tumors
- Resistant FGFR1 and FGFR3 Driven Tumors
#3 - The Development of Targeted Therapy for High Grade Glioma (HGG):
It was first assumed that targeted therapy would be of limited use in HGG given that these very aggressive tumors often have more than one driver However, in certain types of HGG we have shown using targeted therapies (often combined with the anti-autophagy therapy) was a successful approach. Typically children with these tumors would have passed within 6 months. These children are now surviving thanks to the development of targeted therapy (+/- autophagy therapy) thanks to OCF. They have used this knowledge to effectively treat:
- Pleomorphic xantroastrocytoma (PXA)
- NF Driven Glioblastoma
#4 - Exploration of all the Cells in a Low Grade Glioma Using Single Cell Deep Sequencing Techniques (ongoing):
Our research team can now use new sequencing techniques to look at the entire DNA of a single cell. By looking at this for 1000s of cells in a tumor they can obtain an in-depth look at not only what each cell in a tumor is but what each cell is programmed to do. This sequencing has enabled the team to:
- Discover that 40% of a LGG is made up of immune cells and to understand that the immune population is complex with both pro-tumor and anti-tumor populations. This is critical when developing immune therapies to effectively treat these tumors.
- To date OCF's funding has enabled 24 children's tumors to be completely analyzed.
