Developing isoform-selective HSP90 inhibitors for monotherapy and enhanced immunotherapy against lethal prostate cancer
Active Project Grant Awarded Last action
- Award ID
- R01CA297220
- Recipient
-
University Of Notre Dame DU Lac UEI FPU6XGFXMBE9
- Awarding agency
-
National Cancer Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $1,093,452
Award facts
- Assistance listing
- 93.395 Cancer Treatment Research
- Completion date 28% complete
- Place of performance
- Notre Dame, IN 46556, USA
Award details come from USAspending.gov.
Description
- Abstract
- This project focuses on pioneering a novel approach in anti-cancer drug development through the creation and optimization of isoform-selective inhibitors targeting the 90 KDA heat shock protein (HSP90Β). HSP90 is a crucial chaperone protein involved in the maturation of over 400 client proteins, many of which play significant roles in cancer progression. The selective inhibition of HSP90Β over other isoforms offers a promising strategy to mitigate the side effects associated with pan-HSP90 inhibitors, such as ocular, cardio, and dose-escalating toxicities, which have hindered the clinical success of these treatments. The objectives of this research include the development of HSP90Β-selective inhibitors that demonstrate high affinity and selectivity, without inducing the heat shock response (HSR) or causing toxicity, thereby overcoming major challenges faced in clinical trials of pan-HSP90 inhibitors. Preliminary data indicate these inhibitors not only reduce the proliferation of prostate cancer cell lines but also enhance the efficacy of immune checkpoint blockade (ICB) therapy in prostate cancer models, suggesting their potential to transform treatment- resistant cancers into manageable diseases. Novel HSP90Β-inhibitors with improved solubility were created and will be tested in the current study. The specific aims of the project are threefold: 1. To enhance the pharmacological properties of HSP90Β-selective inhibitors for effective in vivo use against cancer, focusing on solubility, permeability, and half-life while preserving specificity. 2. To evaluate the impact of HSP90Β-inhibitors on client protein profiles in comparison with non-selective HSP90 inhibitors, aiming to elucidate mechanisms of action and identify biomarkers for efficacy and resistance. 3. To assess the efficacy and safety of HSP90Β-inhibitors in primary and metastatic castration-resistant prostate cancer (CRPC) models, examining their potential to synergize with ICB therapy and improve immunotherapy outcomes. This research aligns with the national institutes of health's mission to advance science and applications that improve health outcomes. By focusing on the development of selective drug candidates, this project aims to offer new therapeutic options for metastatic CRPC and potentially other cancers, addressing a significant unmet need in oncology. The outcomes of this study are expected to pave the way for clinical trials, contributing to the broader goal of enhancing cancer treatment strategies and patient survival rates.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $541,851 | |
| Original award | $551,601 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| Orlando Health, Inc. | $31,406 | |
| Trustees Of Indiana University | $33,203 |
Quick answers
Who received award R01CA297220?
R01CA297220 was awarded to University Of Notre Dame DU Lac by National Cancer Institute (National Institutes of Health) on June 10, 2025.
How much is award R01CA297220 worth?
$1,093,452 has been obligated on R01CA297220.
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