# Targeting Lysosomal Vulnerabilities in Renal Pathogenesis

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2024 · $456,791

## Abstract

Project Summary/Abstract
Autophagy is frequently upregulated in cancer cells under metabolic stress to recycle
cellular components for protein and ATP synthesis to promote cell survival. Based on its
important roles in maintaining cell viability and inducing resistance to radiation and
chemotherapy, inhibition of autophagy has become a viable therapeutic approach that has
been evaluated in clinical trials. However, there is a need to identify predictive biomarkers
to enable selection of patients that may best respond to autophagy inhibitors. Our
preliminary data demonstrates that the mTORC1 regulator REDD1 controls sensitivity to
autophagy inhibition suggesting that cancers with significant REDD1 levels, such as renal
cell carcinoma (RCC), are hypervulnerable to this therapeutic approach. Our major goal
is to investigate the mechanisms that control sensitivity to autophagy inhibition in RCC
cells to optimize its potential clinical application. In Aim 1, we will determine the role of
REDD1 as a regulator of RCC pathogenesis and sensitivity to autophagy inhibition. In Aim
2, we will investigate the mechanistic link between PIM1 inhibition and upregulation of
REDD1 with a focus on endoplasmic reticular stress. In Aim 3, we will evaluate the impact
of clinically-relevant autophagy inhibitor-based combinations for RCC therapy.

## Key facts

- **NIH application ID:** 10814885
- **Project number:** 5R01CA268383-03
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Jennifer S Carew
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $456,791
- **Award type:** 5
- **Project period:** 2022-02-10 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10814885

## Citation

> US National Institutes of Health, RePORTER application 10814885, Targeting Lysosomal Vulnerabilities in Renal Pathogenesis (5R01CA268383-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10814885. Licensed CC0.

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