# Oncogenic Ras-induced macropinocytosis: A new paradigm for metabolic adaptation

> **NIH NIH R35** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $920,117

## Abstract

Tumors harboring oncogenic Ras mutations are notoriously resistant to existing targeted
therapies. This grave reality coupled with the fact that Ras mutations are prevalent in some of the
deadliest cancers underscore the urgent need to identify new targeting strategies that can be translated
to effective therapies for Ras-driven tumors. The overarching goal of this research program is to
address this need by capitalizing on the emerging paradigm that the metabolic rewiring of Ras tumor
cells constitutes a core vulnerability that can be exploited therapeutically. Specifically, we will pursue a
novel nutrient delivery mechanism that was recently elucidated in my laboratory and is rooted in a
discovery I made earlier in my career that oncogenic Ras stimulates a fluid-phase endocytic process
known as macropinocytosis (MP). We recently discovered that this process is exploited by mutant Ras
cells to internalize extracellular protein and deliver it to where it is degraded to generate free amino
acids that can fuel metabolic pathways. Our studies to date strongly indicate that understanding the
molecular underpinnings of this process and defining its pathophysiological consequences hold
promise for defining new intervention approaches for mutant Ras tumors. We propose to rigorously
test this idea by pursuing three broad questions: 1) How does oncogenic Ras regulate MP? 2) What are
the functional consequences of oncogenic-Ras mediated MP?, and 3) Can MP be exploited as a
therapeutic target? We are uniquely positioned to address these questions owing to the progress we
have made thus far and our access to relevant expertise. We anticipate that this research program will
yield new insights into Ras-dependent oncogenic mechanisms of translational relevance.
.

## Key facts

- **NIH application ID:** 9979778
- **Project number:** 5R35CA210263-05
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** DAFNA BAR-SAGI
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $920,117
- **Award type:** 5
- **Project period:** 2016-09-07 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979778

## Citation

> US National Institutes of Health, RePORTER application 9979778, Oncogenic Ras-induced macropinocytosis: A new paradigm for metabolic adaptation (5R35CA210263-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9979778. Licensed CC0.

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