Biomarkers of dasatinib response and resistance in t-cell acute lymphoblastic leukemia
Active Project Grant Awarded Last action
- Award ID
- R01CA264837
- Recipient
-
ST Jude Children's Research Hospital Inc. UEI JL4JHE9SDRR3
- Awarding agency
-
National Cancer Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $5,973,454
Award facts
- Assistance listing
- 93.394 Cancer Detection and Diagnosis Research
- Completion date 88% complete
- Originally
- Funding
-
- $5,354,407.00 Federal
- $619,047.00 Non-federal
- Place of performance
- Memphis, TN 38105, USA
Award details come from USAspending.gov.
Description
- Abstract
- Acute lymphoblastic leukemia (all) is the most common cancer in children, with t-cell all accounting for 15% of cases. T-all in children is associated with aggressive clinical features and inferior treatment response to combination chemotherapy, compared to b-cell all. Further intensification of cytotoxic drug-based therapy is ineffective for relapsed t-all and novel agents are much needed for these patients. We recently discovered that a significant proportion of pediatric t-all exhibits exceptional response to tyrosine kinase inhibitor dasatinib, in an ABL-independent fashion. Our preliminary genomic analyses pointed to the activation of the pretcr-LCK signaling pathway as a potential driver of this drug response phenotype. We have developed an innovative systems biology approach that integrates transcriptional profile with functional EX vivo drug testing in order to develop a clinically translatable biomarker for sensitivity and resistance to dasatinib in t-all. We hypothesize that our systems biology approach can comprehensively identify molecular determinants of dasatinib response in t-all, and that dasatinib-sensitive t-alls have distinct clinical and genomic features. In this project, we propose to 1) develop a systems biology-based biomarker model of dasatinib sensitivity in t- all; 2) systematically characterize genomics and clinical features associated with dasatinib sensitivity in t-all, and 3) explore mechanism of dasatinib resistance in t-all and develop biomarker-driven combination therapy to overcome drug resistance. Successful completion of these studies is likely to substantially shift the paradigm of how pediatric t-all is treated and significantly impact the next generation of clinical trials and improve cure rates for children with this devastating illness.
Transactions
| Action | Federal | Non-federal | Date |
|---|---|---|---|
| Amendment | $0 | $0 | |
| Amendment | $599,172 | $0 | |
| Amendment | $599,172 | $0 | |
| Amendment | $569,213 | $0 | |
| Amendment | $587,189 | $0 | |
| Amendment | $587,189 | $0 | |
| Amendment | $587,189 | $0 | |
| Amendment | $587,189 | $0 | |
| Amendment | $619,047 | $0 | |
| Original award | $619,047 | $619,047 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| The Washington University | $28,768 | |
| Arietis Corporation | $333,366 | |
| The Children's Hospital Of Philadelphia | $219,120 | |
| University Of Florida | $10,418 | |
| The Children's Hospital Of Philadelphia | $208,164 |
Quick answers
Who received award R01CA264837?
R01CA264837 was awarded to ST Jude Children's Research Hospital Inc. by National Cancer Institute (National Institutes of Health) on July 1, 2021.
How much is award R01CA264837 worth?
$5,973,454 has been obligated on R01CA264837: $5,354,407 in federal funding and $619,047 in non-federal funding.
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