# Co-targeting mTOR and YAP signaling in glioblastoma

> **NIH NIH R01** · GREATER LOS ANGELES VETERANS RESEARCH AND EDUCATION FOUNDATION · 2021 · $326,586

## Abstract

Project Summary
 Glioblastomas are the most common primary malignancy of the central nervous system and are typically
rapidly proliferating tumors resistant to chemotherapeutic intervention. Their complex and heterogeneous
nature has hampered progress towards the development of successful therapies. The mammalian target of
rapamycin (mTOR) kinase and the YAP oncoprotein have recently emerged as an attractive targets for
therapeutic intervention in glioblastoma.
 Two multisubunit complexes containing mTOR exist, mTORC1 and mTORC2 which differ in their
regulatory subunit compositions containing Raptor and Rictor, respectively. While hyperactive mTORC1
activity has been targeted in many cancers, including glioblastoma with limited success, dysregulated
mTORC2 function has only recently begun to be investigated.
 The downstream effector of the Hippo cascade, YAP has been found to be overexpressed in brain cancers
and recently, experimental evidence has supported crosstalk mechanisms coordinating the activities of these
cascades to promote glioblastoma proliferation, motility and invasiveness.
 In this application we propose to 1). identify and characterize glioblastoma-associated activating mutations
in YAP which render this oncoprotein constitutively active, 2). clarify recently identified signaling crosstalk
interactions between mTORC2 and Hippo signaling cascade components and 3.) evaluate a novel YAP-TEAD
specific small molecule inhibitor alone and in combination with mTORC2 specific inhibitors in xenografts and
genetically engineered mouse (GEM) models of the disease. We also propose to investigate and chemically
modify the YAP inhibitor to build in desired anti-glioblastoma effects.

## Key facts

- **NIH application ID:** 10126811
- **Project number:** 6R01CA217820-04
- **Recipient organization:** GREATER LOS ANGELES VETERANS RESEARCH AND EDUCATION FOUNDATION
- **Principal Investigator:** JOSEPH F GERA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $326,586
- **Award type:** 6
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126811

## Citation

> US National Institutes of Health, RePORTER application 10126811, Co-targeting mTOR and YAP signaling in glioblastoma (6R01CA217820-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10126811. Licensed CC0.

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