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The Role of Immature Tumor Subpopulations In Pediatric Rhabdomyosarcoma

Award Number: R01CA262790
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/04/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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The Role of Immature Tumor Subpopulations In Pediatric Rhabdomyosarcoma - PROJECT SUMMARY / ABSTRACT Rhabdomyosarcoma (RMS) is a devastating pediatric soft tissue cancer with morphological features of develop- ing skeletal muscles. Although most patients with RMS achieve a complete remission, one third will develop disease recurrence which is associated with a dismal clinical outcome. These clinical challenges underscore an urgent need to identify patients at risk for resistance and develop better therapy to reduce the risk of recurrence. Our pilot study revealed that rhabdomyosarcoma tumors have developmental intratumoral heterogeneity: differ- ent cells in a single tumor harbor transcriptomic feature of different myogenic stages. Moreover, tumor cells with developmentally immature characteristics are enriched in post-therapy specimens and have the potential to rep- licate and reconstitute the entire developmental trajectory after therapy. In this application, we will develop com- putational analysis methods to unambiguously identify immature tumor subpopulations in single cell RNA-seq data and to reveal their master deregulated genes (Aim 1); In Aim 2, we will characterize the changes in those transcriptional networks and cellular states during treatment in orthoptic patient derived xenograft models (O- PDXs) in vivo. And in Aim 3, we will develop an innovative deep-learning data mining approach to evaluate the prognostic significance of the myogenic transcriptional networks that underly RMS cellular heterogeneity in pa- tient tumors. The proposed study integrates computational, statistical and experimental approaches to study the role of immature cell populations in rhabdomyosarcoma recurrence. Building upon our computational expertise, research experience in rhabdomyosarcoma, robust preliminary results and highly productive collaborations with multi-disciplinary expertise in genomics/epigenomics, machine learning, Bayesian statistics and translational re- search in rhabdomyosarcoma, we are in a unique position to achieve the goals of this research proposal. The proposed research will be impactful because it will potentially change how we treat children with rhabdomyosar- coma and the developed computational/statistical approaches will be broadly applicable to cancer research.


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: 2026 ( Subtotal = $416,325 )
2026	2026	ST JUDE CHILDREN'S RESEARCH HOSPITAL INC	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Cancer Detection and Diagnosis Research	000	5	3/3/2026	NON-COMPETING CONTINUATION	$416,325
														Subtotal = $416,325

Issue Date FY: 2025 ( Subtotal = $416,325 )
2025	2025	ST JUDE CHILDREN'S RESEARCH HOSPITAL INC	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Cancer Detection and Diagnosis Research	000	4	2/13/2025	NON-COMPETING CONTINUATION	$374,693
2025	2025	ST JUDE CHILDREN'S RESEARCH HOSPITAL INC	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Cancer Detection and Diagnosis Research	001	4	5/22/2025	NON-COMPETING CONTINUATION	$41,632
														Subtotal = $416,325

Issue Date FY: 2024 ( Subtotal = $395,510 )
2024	2024	ST JUDE CHILDREN'S RESEARCH HOSPITAL INC	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Cancer Detection and Diagnosis Research	001	3	4/16/2024	NON-COMPETING CONTINUATION	$20,817
2024	2024	ST JUDE CHILDREN'S RESEARCH HOSPITAL INC	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Cancer Detection and Diagnosis Research	000	3	2/7/2024	NON-COMPETING CONTINUATION	$374,693
														Subtotal = $395,510

Issue Date FY: 2023 ( Subtotal = $407,999 )
2023	2023	ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Cancer Detection and Diagnosis Research	000	2	2/28/2023	NON-COMPETING CONTINUATION	$407,999
														Subtotal = $407,999

Issue Date FY: 2022 ( Subtotal = $416,325 )
2022	2022	ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Cancer Detection and Diagnosis Research	000	1	3/4/2022	NEW	$416,325
														Subtotal = $416,325

Grand Total All Awards = $2,052,484

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The Role of Immature Tumor Subpopulations In Pediatric Rhabdomyosarcoma

Award Number: R01CA262790

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/04/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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