# Preclinical-Clinical Trials Collaboration to effectively advance new combination therapies for malignant peripheral nerve sheath tumors

> **NIH NIH U01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $334,967

## Abstract

ABSTRACT
Neurofibromatosis type 1 (NF1) is a prevalent familial cancer syndrome affecting 1 in 3500 individuals worldwide.
The most commonly lethal feature associated with NF1 is malignant peripheral nerve sheath tumors (MPNST).
These soft tissue sarcomas are highly aggressive and frequently metastasize. Despite radiation and
chemotherapy, inoperable tumors rapidly progress and are universally lethal. As such, identifying effective
treatments for MPNST is critical.
The primary goal of this application is to establish a robust preclinical/clinical pipeline (bench-to-bedside and
back) to rapidly develop and test new (combination) therapies for this deadly malignancy. This effort will harness
the specialized expertise of clinical investigators at the NCI and Children’s National Medical Center, extramural
experts in NF1 biology and therapeutic development, and will leverage the unique resources of the NIH Clinical
Center. Specifically, new discoveries of mechanisms that drive NF1-related tumorigenesis together with recent
insights into the immunoreactivity of MPNST will be used to develop rational combination therapies and will be
tested in a robust preclinical MPNST mouse model (Karen Cichowski, BWH, extramural preclinical center).
These insights will then be used to perform clinical trials in MPNST patients with an emphasis on evaluating
more than one combination therapy within the same trial (Brigitte Widemann, NCI, Intramural NIH Clinical Center,
AeRang Kim, Children’s National Medical Center). This will allow for more timely identification of active agents
and will allow patients with this highly refractory disease to have more treatment options available to them.
Furthermore, the preclinical to clinical translation will be complemented by comprehensive genomic and
immunological analyses of tumor samples obtained prior to treatment and on treatment with novel agents in
order to identify mechanisms of response and resistance and to identify additional potential targets for therapy
(Jack Shern, NCI, Intramural NIH). As such, insight and samples from the clinic will serve as the foundation to
develop new or improve existing therapies, thus highlighting the iterative and collaborative nature of this pipeline.
Taken together, we have assembled a multi-disciplinary team of basic and clinical scientists from different fields
to develop and translate promising therapies for individuals with MPNST. This effort includes experts in NF1
biology and therapeutic development, a diverse set of clinicians with expertise in MPNST and immunotherapy,
and genomicists. Importantly, a subset of these investigators already have a track record of working together to
develop new trials for MPNST patients. This grant will allow more effective and rapid translation of promising
new therapies for MPNST and will expand the type of (combination) therapies that are developed, by bringing in
additional expertise and leveraging the unique resources of the NIH Clinical Center. Ul...

## Key facts

- **NIH application ID:** 10909160
- **Project number:** 5U01CA268814-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** KAREN M CICHOWSKI
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $334,967
- **Award type:** 5
- **Project period:** 2022-07-08 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909160

## Citation

> US National Institutes of Health, RePORTER application 10909160, Preclinical-Clinical Trials Collaboration to effectively advance new combination therapies for malignant peripheral nerve sheath tumors (5U01CA268814-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10909160. Licensed CC0.

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