# Project 3: Defining the appropriate context for targeting kinase signaling in combination with androgen receptor blockade to enhance therapeutic response in metastatic prostate cancer

> **NIH NIH U54** · SLOAN-KETTERING INST CAN RESEARCH · 2021 · $455,764

## Abstract

ABSTRACT 
Through bench to bedside translation, we discovered that the PI3K and AR pathways regulate one another in a 
reciprocal and inhibitory fashion through feedback, explaining the limited efficacy of PI3K pathway inhibitors as 
monotherapy in clinical trials of patients with metastatic prostate cancer. Based on our work, the first clinical 
trial of combined PI3K and AR pathway inhibition was recently reported demonstrating a significant benefit for 
combination therapy in patients with tumors harboring loss of PTEN. Our proposal aims to take these exciting 
finding back to the pre-clinical space to 1) define biomarkers of intrinsic sensitivity and resistance to inform 
appropriate patient selection for combination therapy; 2) define the mechanisms of acquired resistance; 3) 
devise therapeutic strategies to overcome resistance; 4) optimize AR pathway targeting in the setting of PI3K 
pathway inhibition to maximize tumor response and 5) explore the therapeutic role of FGFR in a novel subset 
of AR negative prostate cancers.

## Key facts

- **NIH application ID:** 10250363
- **Project number:** 5U54CA224079-04
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Brett Stewart Carver
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $455,764
- **Award type:** 5
- **Project period:** 2017-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10250363

## Citation

> US National Institutes of Health, RePORTER application 10250363, Project 3: Defining the appropriate context for targeting kinase signaling in combination with androgen receptor blockade to enhance therapeutic response in metastatic prostate cancer (5U54CA224079-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10250363. Licensed CC0.

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