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Dr. Kathryn LembergDr. Kathryn Lemberg – Johns Hopkins University

CureSearch Young Investigator Award: 2019-2021

Focus: Malignant Peripheral Nerve Sheath Tumor 

Project Title: JHU395: A glutamine antagonist for malignant peripheral nerve sheath tumor

Project Overview: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive tumors that arise from the cells that normally support nerve function. Most cases are seen with the genetic syndrome neurofibromatosis type 1, but these tumors can also arise without a known cause or as secondary cancers in response to prior radiation therapy. MPNST is the leading cause of mortality in patients with neurofibromatosis type 1 and has a median overall survival in the pediatric population is only 30 months. MPNSTs are incredibly challenging to treat as they are complex and rare. Moreover, they tend to metastasize and do not respond well to chemotherapy or radiation therapy. Surgery is currently the best treatment option for MPNST, but due to the locations that tumors tend to develop, complete surgical removal is challenging. When surgery does not result in the complete removal of the tumor, outcomes are poor and 4-year event-free survival is only 30%.

Dr. Lemberg’s CureSearch-funded project aims to exploit a common characteristic of tumor cells to trigger their destruction. Tumor cells use energy differently than normal cells. To satisfy the high energy demand of tumor cells that are constantly growing and dividing, they are notoriously dependent on a protein building block called glutamine. Dr. Lemberg will attempt to block the ability to use glutamine in order to starve the tumors cells of an essential nutrient. Dr. Lemberg will test a novel glutamine antagonist, JHU395,in MPNST models to determine if it is a feasible treatment strategy. Through this project, Dr. Lemberg ultimately aspires to set a well-characterized, exciting new drug on the path to clinical trials in MPNST patients.

“Pediatric and young adult patients deserve more effective treatments with fewer side effects than have been classically available for these tumors,” said Dr. Lemberg. “As a Young Investigator I look forward to collaborating with others in the CureSearch community to successfully develop new medicines for sarcoma.”

Project Update: As of April 2020: Dr. Lemberg has developed two novel patient-derived MPNST xenografts, models pivotal to the assessment of the efficacy and toxicity of her therapy. In addition, she has developed a novel quantitative metabolite biomarker which will enable her to determine how her innovative metabolism-blocking drug is working in her animal models. Both of these activities have set Dr. Lemberg on an accelerated path toward identifying the optimal dosing of her therapy in MPNST models.

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