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BUILDING TARGETED APPROACHES TO CARE
Dr. Mulcahy Levy’ s work
focuses on two distinct
areas. The first examines the
relationship between BRAF
mutations and autophagy
in treating low- and highgrade
glioma. In a fraction of
patients that are diagnosed
with glioma, the BRAF
gene, which regulates cell
growth, functions incorrectly.
Currently, drugs exist that can
treat this mutation, but a high
percentage of patients either
don’ t respond to the drug or
develop resistance.
Dr. Mulcahy Levy’ s latest study
aimed to understand why and
test a new treatment plan
with the goal of stemming
this resistance. Instead of
treating patients with the
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BRAF mutation drug alone, her study added an autophagy inhibitor to the mix. That drug, which blocks the body’ s cell recycling process, seemed to not only stave off and reverse resistance, but also boost the BRAF-targeted drug.
“ High-grade glioma patients have really dismal survival outcomes, so the work is to really extend the life of those patients. But even in our low-grade glioma patients who don’ t have quite as much risk of death, they have an incredibly high risk of longterm complications and side effects from treatment,” Dr. Mulcahy Levy explains.“ Using this combination therapy as a way to get these tumor cells to die so that they don’ t have to undergo multiple rounds of
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different kinds of treatment, can save them late effects, short-term side effects and the requirement of being in treatment for eight years or more of their life.”
A clinical trial based on Dr. Mulcahy Levy’ s work is ongoing through the Pediatric Brain Tumor Consortium and was the first collaborative autophagy inhibition trial in pediatrics. She continues to collaborate with experts across the country, drawing on expertise and samples from New York University, Johns Hopkins University and University of California, San Francisco, among others.
Dr. Mulcahy Levy’ s work extends to ATRT as well. Her team is currently using CRISPR gene editing technology to screen these tumors for
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potential druggable targets.
This work identified a gene
known as CDK7 as a promising
pathway for further study.
She’ s working with Dr. Dahl,
who is employing similar
techniques to study
DIPG tumors, to push this
work forward.
SEARCHING FOR NEW HOPE
Instead of using CRISPR, Dr.
Dahl’ s research employed
an shRNA screen, which he
describes as an unbiased
method for probing hundreds
of genes simultaneously in the
hopes of finding a new way to
kill DIPG tumors. That hunt led
his team to CDK9, a proteincoding
gene that regulates
transcription.
“ DIPGs are defined by a
particular mutation called
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