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The role of Olig2 in the tumorigenesis, progression and metastasis in MYC-amplified medulloblastoma

Award Number: R01CA241192
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/07/2019
PERIOD OF PERFORMANCE END DATE: 07/31/2024

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The role of Olig2 in the tumorigenesis, progression and metastasis in MYC-amplified medulloblastoma - Project Summary Medulloblastoma (MB) is the most common malignant brain tumor in children. Although treatment combining surgery, radiation and high-dose chemotherapy has led to increased survival rates, many MB patients still die from the disease. Moreover, surviving patients suffer severe long-term side effects as a consequence of treatment. It is therefore crucial to develop more effective and less toxic therapies. The most aggressive subtype of MB consists of tumors that exhibit amplification of the MYC oncogene. Patients with MYC-amplified MB exhibit a high frequency of tumor dissemination to the entire brain and spinal cord, often experience treatment resistance and have extremely poor prognoses. In this application, we propose to use novel mouse MYC-driven MB and patient-derived xenograft (PDX) models to investigate the role of oligodendrocyte lineage transcription factor 2 (Olig2) in tumorigenesis, progression and metastasis of MYC-amplified MB. We will use these mouse models to evaluate a novel targeted approach to treatment. To accomplish this we will: (1) evaluate whether ablation of Olig2+ tumor cells can prevent tumor formation, progression and metastasis, (2) determine whether deletion of the Olig2 gene prevents tumor progression and metastasis, and (3) test the prediction that targeting Olig2 with a small molecule inhibitor can inhibit growth and prevent metastasis in a human MYC-amplified MB PDX model. If these studies are successful, they will help identify new targeted therapies that can be effective in treating patients with MYC-amplified MB.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $398,055 )
2023	2023	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Cancer Treatment Research	000	5	9/14/2023	NON-COMPETING CONTINUATION	$398,055
														Subtotal = $398,055

Issue Date FY: 2022 ( Subtotal = $398,055 )
2022	2022	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Cancer Treatment Research	000	4	7/19/2022	NON-COMPETING CONTINUATION	$398,055
														Subtotal = $398,055

Issue Date FY: 2021 ( Subtotal = $406,178 )
2021	2021	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Cancer Treatment Research	000	3	8/13/2021	NON-COMPETING CONTINUATION	$406,178
														Subtotal = $406,178

Issue Date FY: 2020 ( Subtotal = $410,439 )
2020	2020	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Cancer Treatment Research	000	2	7/30/2020	NON-COMPETING CONTINUATION	$410,439
														Subtotal = $410,439

Issue Date FY: 2019 ( Subtotal = $419,875 )
2019	2019	CHILDREN'S RESEARCH INSTITUTE	111 MICHIGAN AVE NW	WASHINGTON	DC	20010	DISTRICT OF COLUMBIA	USA	Cancer Treatment Research	000	1	8/7/2019	NEW	$419,875
														Subtotal = $419,875

Grand Total All Awards = $2,032,602

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The role of Olig2 in the tumorigenesis, progression and metastasis in MYC-amplified medulloblastoma

Award Number: R01CA241192

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/07/2019

PERIOD OF PERFORMANCE END DATE: 07/31/2024

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