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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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