Profilin as a novel target for vascular normalization in renal cancer
Active Project Grant Awarded Last action
- Award ID
- R00CA267180
- Recipient
-
University Of Pittsburgh - Of The Commonwealth System Of Higher Education UEI MKAGLD59JRL1
- Awarding agency
-
National Cancer Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $996,000
Award facts
- Assistance listing
- 93.396 Cancer Biology Research
- Completion date 74% complete
- Place of performance
- Pittsburgh, PA 15213, USA
Award details come from USAspending.gov.
Description
- Abstract
- Abstract renal cell carcinoma (RCC) is estimated to result in 76,080 new cases and 13,780 deaths in 2021. Clear cell renal cell carcinoma (CCRCC) is the most common subtype of RCC (>75% of RCC patients) and is characterized by a high vascularized tumor microenvironment (TME). Anti- angiogenic and vascular normalization (VN) inducing therapies are initially effective, almost all patients develop resistance to these therapies. Therefore, there is a need to identify alternative fundamental therapies for CCRCC. Our lab and others have demonstrated that actin cytoskeleton plays a key role in regulation of vascular endothelial cell (VEC) in angiogenesis and barrier function. Furthermore, IT has been demonstrated that PROFILIN1 (PFN1) is an important regulator of actin-driven processes such as cell migration and proliferation (including in VEC, affecting angiogenic potential). PFN1 is also overexpressed in human CCRCC and higher expression of PFN1 has been linked to poor clinical outcome and advanced disease features. The goal of this study is to further demonstrate PFN1'S fundamental role in regulation of progression of CCRCC through modulation of tumor- promoted vascularization and that PFN1 serves as a therapeutic target for RCC. Our preliminary data demonstrates that overexpressed PFN1 is primarily found in tumor-associated VEC (TAEC). We further demonstrate that loss of PFN1 by genetic deletion in vivo or inhibition of PFN1 by small molecule inhibitor reduces aberrant vascularization in various pathological settings (including retina and kidney) and attenuates RCC progression in vivo. Aim 1 of this proposal seeks to test a postulate that endothelial PFN1 promotes a pro- tumorigenic TME driving tumor progression in CCRCC and can be diminished by tumor-localized delivery of novel small molecule antagonist of PFN1-actin interaction. Aim 2 of this proposal will test a postulate that PFN1 regulates the intrinsic angiogenic capability of VEC through augmenting mitochondrial function. Aim 3 tests a postulate that VEC-secreted PFN1 acts as a paracrine signaling mediator to promote CCRCC aggressiveness. Aims 1 and 2 will mostly be performed in the K99 mentored stage, during which I will continue my training in contrast-enabled ultrasound, immuno-, and mitochondrial biology. These trainings will be pivotal in my transition to independence in the R00 stage where aim 3 and the rest of aim 2 will be executed.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $249,000 | |
| Amendment | $249,000 | |
| Amendment | $0 | |
| Amendment | $249,000 | |
| Amendment | $249,000 | |
| Original award | $249,000 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| University Of Pittsburgh - Of The Commonwealth System Of Higher Education | $47,700 |
Quick answers
Who received award R00CA267180?
R00CA267180 was awarded to University Of Pittsburgh - Of The Commonwealth System Of Higher Education by National Cancer Institute (National Institutes of Health) on August 28, 2024.
How much is award R00CA267180 worth?
$996,000 has been obligated on R00CA267180.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award