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Determining how neuroblastoma cell state evades standard of care chemotherapy and drives tumor recurrence

Award Number: F31CA306336
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 06/16/2026
PERIOD OF PERFORMANCE END DATE: 06/15/2029

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Determining how neuroblastoma cell state evades standard of care chemotherapy and drives tumor recurrence - ABSTRACT Over 50% of patients with neuroblastoma (NBL) relapse with therapy resistant tumors. The 5-year survival rate of NBL relapse is less than 10%. NBL tumors are heterogeneous and made up of two major cell populations derived from proliferating sympathoblasts: mesenchymal (MES) and adrenergic (ADRN). The overall objective is to determine how the developmental hierarchy of the neural crest cells contribute to NBL recurrence. My central hypothesis is that the MES cell population evades standard of care treatments and re- establishes tumor recurrence in NBL. To determine the lineage relationship between ADRN and MES cells, barcoding orthotopic patient derived xenograft (O-PDX) models, 3D spheroid models, and fluorescence- activated cell sorting to purify cell states will be performed. From these studies, I anticipate understanding the origins between the two primary cell states and determine which cell state drives tumor formation of NBL. To identify underlying cell states that are resistant to chemotherapy, standard of care (SOC) chemotherapy for relapsed tumors will be performed in mice and 3D spheroids and single-cell RNA sequencing will be performed to analyze changes to cell populations during treatment. High-content screening of 3D spheroids will also be utilized. From these studies, I anticipate determining the cell population resistant to chemotherapeutics and identify the cell state that drives tumor recurrence. There is a drastic need for understanding the cellular makeup and features of relapsed NBL tumors. To start bridging the gaps within the field, I propose a study to comprehensively understand the developmental origins of NBL and the lineage relationship between ADRN and MES cell populations. These studies are designed to determine how the tumors repopulate and may lead to a novel way to treat relapsed NBL tumors.


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 = $49,114 )
2026	2026	ST. JUDE CHILDREN'S RESEARCH HOSPITAL GRADUATE SCHOOL OF BIOMEDICAL SCIENCES, LLC	262 DANNY THOMAS PL # 1500	MEMPHIS	TN	38105	SHELBY	USA	Cancer Research Manpower	000	1	6/16/2026	NEW	$49,114
2026	2026	ST. JUDE CHILDREN'S RESEARCH HOSPITAL GRADUATE SCHOOL OF BIOMEDICAL SCIENCES, LLC	262 DANNY THOMAS PL # 1500	MEMPHIS	TN	38105	SHELBY	USA	Cancer Research Manpower	001	1	6/16/2026	NEW	$0
														Subtotal = $49,114

Grand Total All Awards = $49,114

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Determining how neuroblastoma cell state evades standard of care chemotherapy and drives tumor recurrence

Award Number: F31CA306336

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 06/16/2026

PERIOD OF PERFORMANCE END DATE: 06/15/2029

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