Elucidating molecular and epigenetic drivers of pathological angiogenesis in choroid plexus carcinoma
Active Project Grant Awarded Last action
- Award ID
- F30CA306135
- Recipient
-
President And Fellows Of Harvard College UEI JDLVAVGYJQ21 Part of Harvard College President & Fellows Of
- Awarding agency
-
National Cancer Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $86,650
Award facts
- Assistance listing
- 93.398 Cancer Research Manpower
- Completion date 0% complete
- Originally
- Place of performance
- Boston, MA 02115, USA
Award details come from USAspending.gov.
Description
- Abstract
- Choroid plexus carcinoma (CPC) is an aggressive, rare cancer arising from the brain's choroid plexus (CHP), a dynamic, highly vascularized, cerebrospinal fluid-secreting tissue. CPC is most common in young children, and five-year overall survival estimates continue to fall under ~50%. The only reliable prognostic factor is the extent of surgical resection. Unfortunately, CPC typically presents with large, extremely vascularized tumors that extend into adjacent brain tissue. These factors increase risk of incomplete surgical resection and intraoperative hemorrhage. We believe that preoperative decreases in CPC vascularity would lead to better outcomes for patients, including survival and quality of life. Our leading hypothesis is that selective, cancer-specific vulnerabilities in the interactions between epithelial and vascular cells in CPC can be therapeutically targeted for this purpose. The studies proposed here will focus primarily on targeting MYC, a master transcription factor whose overexpression drives two different mouse models of CPC in our lab, and whose upregulation we have also observed in higher-grade CHP patient tumors. In aim 1, I will map the topography of angiogenesis in the healthy CHP as compared with CPC, completing immunostaining and vascular casting pipelines and supplementing this work with angiogenesis marker panels across development. In aim 2A, I will conduct multiomic analyses of mouse and patient CPC tissue to reveal MYC-specific contributions to regionalized tumor and vascular development in the CHP. This will include MYC-targeted cut & run in combination with single-cell RNA sequencing of mouse tumors compared with patient tumors sequenced via smart-SEQ2. Finally, in aim 2B, I will deliver chronic treatment of direct inhibitors of MYC and its molecular partners to our CPC model mice, and assess vascular alterations via immunostaining, vascular casting, and angiogenesis panels. Ultimately, understanding how CPC vasculature differs from that of the healthy CHP-especially related to MYC-through these aims should identify vulnerable targets as well as critical periods in the time course of this rapidly progressing disease, thereby informing development of novel, and necessary, neoadjuvant chemotherapies.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $43,325 | |
| Amendment | $0 | |
| Original award | $43,325 |
Quick answers
Who received award F30CA306135?
F30CA306135 was awarded to President And Fellows Of Harvard College by National Cancer Institute (National Institutes of Health) on December 1, 2026.
How much is award F30CA306135 worth?
$86,650 has been obligated on F30CA306135.
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