# Novel regulators of Gli-driven medulloblastoma

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $340,037

## Abstract

Project Abstract
The Sonic Hedgehog (SHH) signaling pathway plays critical roles in the genesis of a large number of human
cancers, including medulloblastoma. To date, the majority of small molecule inhibitors that block SHH signaling
have targeted the pivotal upstream activator Smoothened (SMO), which regulates the levels and activity of the
GLI family of transcription factors. Two of these compounds, including vismodegib, are FDA-approved for
metastatic basal cell carcinoma patients, and are now undergoing clinical evaluation in MB patients. However,
inherent resistance due to mutations downstream of SMO, or rapid tumor recurrence, has already been
frequently observed in MB patients treated with vismodegib. Further, genomic analysis of relapsed, vismodegib
resistant basal cell carcinomas has revealed similar mechanisms of cross-resistance to structurally diverse SMO
inhibitors. Such data highlight the urgent need for targeted therapies with distinct mechanisms of action, with
which to treat patients harboring SHH-driven cancers and to prevent their tumor recurrence. The goal of this
proposal is to identify and characterize a novel set of such regulators (Aims 1 & 2), and to validate their in vivo
roles using mouse and human orthotopic mouse models of MB (Aim 3). The work proposed herein will address
the substantial clinical need for novel druggable targets in SHH-driven cancers. The combined experience of our
team, our extensive unpublished findings, and the unique resources we bring to this project will prove pivotal in
successful completion of the proposed Aims.

## Key facts

- **NIH application ID:** 10018957
- **Project number:** 5R01NS110591-02
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** DAVID J ROBBINS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $340,037
- **Award type:** 5
- **Project period:** 2019-09-17 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018957

## Citation

> US National Institutes of Health, RePORTER application 10018957, Novel regulators of Gli-driven medulloblastoma (5R01NS110591-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10018957. Licensed CC0.

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