# MEK PATHWAY INHIBITION COMBINED WITH 5-AMINOLEVULINIC ACID-PHOTODYNAMIC THERAPY FOR THE TREATMENT OF DIFFUSE MIDLINE GLIOMA

> **NIH NIH F31** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $46,592

## Abstract

PROJECT SUMMARY
Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPG), are deleterious malignant
pediatric tumors of the brainstem. DMG is the leading cause of death among pediatric brain tumors and the
second most common malignant brain cancer afflicting children. DMG has a dismal prognosis of less than 1%
survival within a year of diagnosis, even when using the most aggressive treatments. Approximately 400 children
will be diagnosed with DIPG in the United States in 2022, all of whom will have a median survival of between 8
and 11 months. DMG disease outcomes have plateaued over the past decade due to the lack of effective
treatments and limited diagnostic tools. Many failed clinical trials and therapeutic strategies in DMG can be
attributed to two critical concerns: 1) the selectively penetrable blood brain barrier (BBB) restricts drug delivery
to central nervous system, and 2) despite there being distinct genetic alterations between DMG and adult high-
grade gliomas (aHGG), the agents considered for DMG clinical trials have been derived by extrapolation from
aHGG data, without grounds for the therapeutic translation. Studies have revealed extracellular signal-regulated
protein kinases (ERK), a downstream receptor tyrosine kinase of mitogen-activated protein kinase (MEK), is
upregulated in DMG, raising questions about whether targeting the MAPK/ERK pathway can have anti-tumor
effects in DMG. Targeting MEK in combination with aminolevulinic acid-photodynamic therapy (5-ALA-PDT) is
of interest because inhibition of MEK has been found to significantly enhance protoporphyrin IX (PpIX)
accumulation in vitro and in vivo in a tumor-specific manner. This proposal uses an innovative multimodal
treatment approach that addresses the barriers to successful DMG clinical trials and exploits the molecular
composition of DMG cells to reduce morbidity and mortality. By targeting MEK and employing 5-ALA-PDT, we
anticipate MEK inhibition will synergize with 5-ALA-PDT efficacy by eliciting direct tumor cell killing, vascular
shutdown and immune response, ultimately increasing overall patient survival. If successful, this treatment can
be applied to other inoperable CNS tumors.

## Key facts

- **NIH application ID:** 10536455
- **Project number:** 1F31CA275290-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Gabrielle Alexia Price
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,592
- **Award type:** 1
- **Project period:** 2022-09-26 → 2026-09-25

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10536455

## Citation

> US National Institutes of Health, RePORTER application 10536455, MEK PATHWAY INHIBITION COMBINED WITH 5-AMINOLEVULINIC ACID-PHOTODYNAMIC THERAPY FOR THE TREATMENT OF DIFFUSE MIDLINE GLIOMA (1F31CA275290-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10536455. Licensed CC0.

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