Determining how neuroblastoma cell state evades standard of care chemotherapy and drives tumor recurrence
Active Project Grant Awarded Last action
- Award ID
- F31CA306336
- Recipient
-
ST. Jude Children's Research Hospital Graduate School Of Biomedical Sciences, LLC UEI MN2LFZNE4HH3
- Awarding agency
-
National Cancer Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $98,228
Award facts
- Assistance listing
- 93.398 Cancer Research Manpower
- Completion date 0% complete
- Originally
- Place of performance
- Memphis, TN 38105, USA
Award details come from USAspending.gov.
Description
- 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.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $49,114 | |
| Amendment | $0 | |
| Original award | $49,114 |
Quick answers
Who received award F31CA306336?
F31CA306336 was awarded to ST. Jude Children's Research Hospital Graduate School Of Biomedical Sciences, LLC by National Cancer Institute (National Institutes of Health) on December 15, 2026.
How much is award F31CA306336 worth?
$98,228 has been obligated on F31CA306336.
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