Tuesday, May 13, 2025 5/13/2025

Targeted Therapy in Ex Vivo Medulloblastoma

Award Number: R01CA114567
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Description

Targeted Therapy in Ex Vivo Medulloblastoma - PROJECT SUMMARY/ABSTRACT I lead the Children’s Oncology Group Phase III clinical trial, ACNS0332, which evaluates treatment options for children with high-risk medulloblastoma (the most common pediatric brain tumor) and supratentorial primitive neuroectodermal tumors (sPNETs). The study opened in 2007 and underwent a major amendment in 2014, when emerging data revealed biological disparity between medulloblastomas and sPNETs as well as heterogeneity in sPNET patients. We discontinued sPNET patient enrollment, and genomic analyses funded by the prior cycle of this grant, revealed that 71% of the non-pineal sPNET patients were actually high grade glioma, ependymoma or atypical teratoid rhabdoid tumors, despite sPNET appearance by histopathology. This reveals the limitations of traditional histopathology and shows that contemporary genomic analyses could spare many children from receiving craniospinal irradiation that is not necessary and not helpful. In Aim 1 of this renewal application, we extend the genomic studies to the 300 medulloblastoma patients in the study. We collected research tissue from over 95% of these patients and anticipate that the studies will reveal 1) patient groups who are likely to die from their disease despite the intense therapy on ACNS0332, 2) patient groups that were placed on ACNS0332 because of clinical or histopathologic observations that may include a mixture of good prognosis patients (e.g., those who would fare well with much less radiation than provided on ACNS0332) as well as those with genomically-predicted poor prognosis, who should be stratified differently in the future. In Aim 2 we address the radiation resistance phenotype of the worst prognosis patients, particularly those with amplified MYC or MYCN. We will collect pre- and post-radiation specimens from patient-derived orthotopic xenograft (PDOX) models (14 MYC/MYCN amplified) that we generated and characterized in the prior cycle of this grant; other PDOX models that we receive from four collaborators; and matching cell lines that we generated and characterized. We will use the cell lines for to screen FDA approved drugs for those that overcome radiation resistance and to conduct functional genomic screens to identify pathways that, when inhibited, convert radiation resistant cells into radiation sensitive cells. In vivo efficacy studies on PDOX mouse models representing dozens of patients will follow. The significance is that this work will likely reduce unnecessary radiation exposure to patients who do not warrant high-dose craniospinal irradiation, identify patients who would best be served by alternative therapies, and generate pre-clinical data to prioritize the most effective agents for upcoming human clinical trials.


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: 2025 ( Subtotal = $0 )
2025	2023	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Cancer Treatment Research	000	15	4/10/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $576,160 )
2023	2023	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Cancer Treatment Research	000	15	2/10/2023	NON-COMPETING CONTINUATION	$438,734
2023	2023	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Cancer Treatment Research	001	15	2/15/2023	SUPPLEMENT FOR EXPANSION	$137,426
														Subtotal = $576,160

Issue Date FY: 2022 ( Subtotal = $701,649 )
2022	2022	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Cancer Treatment Research	011	14	5/20/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$35,817
2022	2022	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Cancer Treatment Research	004	14	2/8/2022	SUPPLEMENT FOR EXPANSION	$125,368
2022	2022	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Cancer Treatment Research	009	14	3/31/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$104,835
2022	2022	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Cancer Treatment Research	003	14	2/2/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$402,919
2022	2022	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Cancer Treatment Research	010	14	5/20/2022	SUPPLEMENT FOR EXPANSION	$11,142
2022	2022	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Cancer Treatment Research	006	14	2/15/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2022	2022	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Cancer Treatment Research	005	14	2/15/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	008	13	3/31/2022	SUPPLEMENT FOR EXPANSION	-$69,886
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	001	13	2/2/2022	NON-COMPETING CONTINUATION	$0
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	007	13	3/31/2022	NON-COMPETING CONTINUATION	-$34,949
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	002	13	2/2/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Detection and Diagnosis Research	012	12	6/29/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Detection and Diagnosis Research	000	12	1/6/2022	SUPPLEMENT FOR EXPANSION	$126,403
														Subtotal = $701,649

Issue Date FY: 2021 ( Subtotal = $364,143 )
2021	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	005	13	9/17/2021	SUPPLEMENT FOR EXPANSION	$69,886
2021	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	002	13	1/25/2021	NON-COMPETING CONTINUATION	$21,033
2021	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	001	13	11/25/2020	NON-COMPETING CONTINUATION	$399,627
2021	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Detection and Diagnosis Research	003	12	3/26/2021	SUPPLEMENT FOR EXPANSION	-$126,403
2021	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Detection and Diagnosis Research	000	12	10/21/2020	SUPPLEMENT FOR EXPANSION	$0
2021	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Detection and Diagnosis Research	004	12	7/26/2021	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $364,143

Issue Date FY: 2020 ( Subtotal = $596,660 )
2020	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	12	1/8/2020	NON-COMPETING CONTINUATION	$420,660
2020	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Detection and Diagnosis Research	001	12	9/14/2020	SUPPLEMENT FOR EXPANSION	$176,000
														Subtotal = $596,660

Issue Date FY: 2019 ( Subtotal = $438,710 )
2019	2019	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	11	12/26/2018	COMPETING CONTINUATION	$438,710
2019	2019	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	001	11	4/11/2019	COMPETING CONTINUATION	$0
														Subtotal = $438,710

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2016	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	10	9/14/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	10	6/14/2017	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $227,292 )
2016	2016	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	10	3/28/2016	EXTENSION WITH OR WITHOUT FUNDS	$227,292
														Subtotal = $227,292

Issue Date FY: 2015 ( Subtotal = $227,292 )
2015	2015	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	9	3/18/2015	NON-COMPETING CONTINUATION	$227,292
														Subtotal = $227,292

Issue Date FY: 2014 ( Subtotal = $220,474 )
2014	2014	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	8	6/9/2014	NON-COMPETING CONTINUATION	$220,474
														Subtotal = $220,474

Issue Date FY: 2013 ( Subtotal = $213,654 )
2013	2013	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	7	3/7/2013	NON-COMPETING CONTINUATION	$102,281
2013	2013	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	001	7	6/28/2013	NON-COMPETING CONTINUATION	$111,373
														Subtotal = $213,654

Issue Date FY: 2012 ( Subtotal = $227,292 )
2012	2012	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	6	4/18/2012	COMPETING CONTINUATION	$227,292
														Subtotal = $227,292

Issue Date FY: 2010 ( Subtotal = $223,417 )
2010	2010	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Cancer Detection and Diagnosis Research	001	5	1/22/2010	NON-COMPETING CONTINUATION	$22,341
2010	2010	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Cancer Detection and Diagnosis Research	000	5	11/20/2009	NON-COMPETING CONTINUATION	$201,076
														Subtotal = $223,417

Grand Total All Awards = $4,913,755

Page 1 of 2 (59 items)12

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Targeted Therapy in Ex Vivo Medulloblastoma

Award Number: R01CA114567

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer