Stories about: brain tumors

Solving the DIPG puzzle a single cell at a time

Image depicting the cellular makeup of DIPG/DMG tumors vs normal brain tissue development
Scientists have discovered that DIPG/DMG tumors are made up of H3K27M-mutated cell populations that contain many cells stuck in a stem-cell-like state, fueling tumor growth. Cells that can differentiate despite the H3K27M mutation could hold the key to unlocking a new therapy for DIPG/DMG.

For more than 15 years, pediatric neuro-oncologist Mariella Filbin, MD, PhD, has been on a scientific crusade to understand DIPG (diffuse intrinsic pontine glioma). She hopes to one day be able to cure a disease that has historically been thought of as an incurable type of childhood brain cancer.

“While I was in medical school, I met a young girl who was diagnosed with DIPG,” Filbin recalls. “When I heard that there was no treatment available, I couldn’t believe that was the case. It really made a huge impression on me and since then, I’ve dedicated all my research to fighting DIPG.”

Her mission brought her to Boston Children’s Hospital for her medical residency program and later, to do postdoctoral research at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Now, she’s starting her own research laboratory focused on DIPG — which has also been called diffuse midline glioma (DMG) in recent years — and continuing to treat children with brain tumors at the Dana-Farber/Boston Children’s pediatric brain tumor treatment center. She’s also a scientist affiliated with the Broad Institute Cancer Program.

This year, Filbin has made new impact in the field by leveraging the newest single-cell genetic sequencing technologies to analyze exactly how DIPG develops in the first place. Her latest research, published in Science, entailed profiling more than 3,300 individual brain cells from biopsies of six different patients.

Using what’s known as a single-cell RNA sequencing approach to interrogate the makeup of DIPG/DMG tumors, Filbin was able to identify a particularly problematic type of brain cell that acts forever young, constantly dividing over and over again in a manner similar to stem cells.

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Webchat to highlight what’s new in pediatric brain tumors

pediatric brain tumors, child MRI

Last September, the National Center for Health Statistics reported that brain tumors have overtaken the much more common leukemia as the leading cause of death from pediatric cancer. Although progress has been made and the promise of more progress is on the horizon, the cure rate for childhood brain tumors lags behind a number of other pediatric cancers.

As pediatric neuro-oncologist Peter Manley, MD, of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center told Live Science, new research on cancer genomics “is so impressive that my feeling is that we will continue to see a decline in deaths.”

To mark Brain Tumor Awareness Month, Mark Kieran, MD, PhD, clinical director of the Brain Tumor Center at Dana-Farber/Boston Children’s, will host a webchat on Monday, May 22 (3:30 p.m. ET). The live chat will highlight the latest research and treatments for pediatric brain tumors. Here’s a look back at some recent developments:

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One family, one researcher: How Mikey’s journey is fueling an attack on DIPG

Picture of Mikey on 11th birthday, shortly after his DIPG diagnosis
Mikey and his family at his 11th birthday party, just one week after he was diagnosed with DIPG, a devastating tumor in his brain stem. Since Mikey’s passing in 2008, his family has been committed to supporting DIPG research.

“It’s a brutal disease; there’s just no other way to describe DIPG,” says Steve Czech. “And what’s crazy is that there aren’t many treatment options because it’s such a rare, orphan disease.”

Czech’s son, Mikey, was diagnosed with a diffuse intrinsic pontine glioma (DIPG) on Jan. 6, 2008. It was Mikey’s 11th birthday. The fast growing and difficult-to-treat brainstem tumors are diagnosed in approximately 300 children in the U.S. each year.

Sadly, the virtually incurable disease comes with a poor prognosis for most children. The location of DIPG tumors in the brainstem — which controls many of the body’s involuntary functions, such as breathing — has posed a huge challenge to successful treatment thus far.

“Typically, they give kids about nine months,” says Czech. “Our lives changed forever the day that Mikey was diagnosed.”

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Pediatric brain tumor genomics arrives, as the need for new therapies grows

Allison was the first pediatric brain tumor patient in the world to receive a treatment targeting the BRAF mutation, originally developed to treat adults with melanoma who have the same mutation.

Precision cancer medicine – the vision of tailoring diagnosis and treatments to a tumor’s genetic susceptibilities – is now ready to impact the care of a majority of children with brain tumors. The molecular “signatures” of brain tumors were first characterized in 2002 in a study led by researchers at Boston Children’s Hospital. This has led to the creation of new tumor subgroups and changes in cancer treatment: For example, a current clinical trial is testing the anti-melanoma drug dabrafenib in a variety of brain tumors with the same BRAF mutation – including metastatic anaplastic astrocytoma and low-grade glioma.

In the largest study of its kind to date, investigators at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center genetically tested more than 200 brain tumor samples. They found that many had genetic irregularities that could guide treatment, in some cases with approved drugs or agents being evaluated in clinical trials.

The findings, reported online today by the journal Neuro-Oncology, also demonstrate that testing pediatric brain tumor tissue for genetic abnormalities is clinically feasible.

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Pediatric brain tumor responding well to melanoma drug, targeting a shared mutation

low grade glioma dabrafenib

When Danny Powers showed gross motor delays and poor balance as a toddler, early intervention specialists told his mother, Christi, that the problem was likely weak muscle tone. But when Danny developed severe headaches at age 4 during a family vacation, Christi took him to a local emergency room, where a CT scan revealed a mass in his head. His eventual diagnosis back home in Massachusetts was low-grade glioma, the most common pediatric brain tumor.

Fortunately, low-grade gliomas are non-malignant, slow-growing and highly curable, and most children can look forward to decades of survival. Unfortunately, the standard treatment — chemotherapy and, in some cases, radiation, in addition to surgery — is toxic and can damage the developing brain and body. Moreover, the tumors often regrow, requiring retreatment. By the time Danny was 13, he had been treated twice with surgery and once with a year of chemotherapy, which Mark Kieran, MD, PhD, clinical director of the Brain Tumor Center at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, likens to carpet bombing.

Instead of undergoing another course of chemotherapy when his tumor regrew yet again, Danny entered a clinical trial of a new, targeted drug that acts more like a guided missile — aimed directly at his cancer-causing mutation. 

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Beyond appearances: Molecular genetics revises brain tumor classification and care

What a brain tumor looks like isn’t the best predictor of prognosis. (Jensflorian/Wikimedia Commons)
What a brain tumor looks like isn’t the best predictor of prognosis. (Jensflorian/Wikimedia Commons)

Scott PomeroyScott Pomeroy, MD, PhD, is Neurologist-in-Chief at Boston Children’s Hospital. He practices in the Brain Tumor Center and is a member of the F.M. Kirby Neurobiology Center.

For almost a century, brain tumors have been diagnosed based on their appearance under a microscope and classified by their resemblance to the brain cells from which they are derived. For example, astrocytoma ends with “-oma” to designate that it is a tumor derived from astrocytes. In some cases, especially in children, brain tumors resemble cells in the developing brain and are named for the cells from which they are presumed to arise, such as pineoblastoma for developing cells within the pineal gland or medulloblastoma for developing cells within the cerebellum or brainstem.

In June, the World Health Organization (WHO), which sets the worldwide standard, released an updated brain tumor classification scheme that, for the first time, includes molecular and genetic features.

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Search for brain tumor biomarkers in urine strikes gold

Urine Vascular Biology Program netrin brain tumor biomarker Edward Smith Michael Klagsbrun

A good biomarker is one whose levels go up or down as a patient’s disease worsens or wanes. A great biomarker also gives key insights into disease development. A really great biomarker does both of these things and also serves as a treatment target.

With a protein called netrin-1, Edward Smith, MD, and Michael Klagsbrun, PhD, seem to have hit the trifecta. In a recent paper in Cancer Research, they report a clear relationship between urine netrin levels and medulloblastoma, the most common malignant brain tumor of children.

And show that netrin fuels the tumor’s invasion into healthy brain tissue.

And that blocking netrin may, at least in the laboratory, check the tumor’s spread.

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Re-imagining neurosurgery: Designing a curvy robot

(Photo: Katherine Cohen)
A lab at Boston Children's Hospital hopes to make neurosurgery as minimally invasive as possible. (Photo: Katherine Cohen)
When Patrick Codd, MD, removed a toddler’s deep brain tumor not long ago at Massachusetts General Hospital, he first put a catheter inside the boy’s head to drain the excess fluid that had built up. He and the neurosurgery team then removed a large portion of the child’s skull, exposed the brain and dissected through the brain tissue, using a microscope, until he could reach the tumor, which the team then removed.

The boy is doing fine, but Codd and his mentors at Boston Children’s Hospital—Joseph Madsen, MD, and Pierre Dupont, PhD, chief of Pediatric Cardiac Bioengineering—had a vision: Could the tumor have been removed via the same catheter that he used to drain the fluid, leaving the rest of the brain intact?

Standard surgical techniques—and even newer ones that use lasers or go into the brain through the nose—require surgeons to bore through brain tissue to get to their destination. This carries a risk of injuring sensitive areas as they pass through, like the structures involved in language, as well as a risk for wound infections and complications from extended anesthesia times.

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A day in the life: A pediatric neurosurgeon’s vision

Ed Smith explains the moyamoya operation during a live webcast.

Lindsay Hoshaw contributed to this post.

It’s 7 a.m. and neurosurgeon
Ed Smith, MD
, is downing a Diet Coke as he reviews the MRIs of today’s patients. He sprints up a stairwell to greet his first patient in the pre-operating wing.

Thirteen-year-old Maribel Ramos, about to have brain surgery at Boston Children’s Hospital, sits in her bed fidgeting. Smith reassures her about the operation, promises they’ll shave off as little hair as possible, and gets Maribel to crack a smile by telling her he moonlights as a hairdresser.

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Not all brain tumors are made the same, and that’s important

medulloblastoma
(saeru/Flickr)

When you look at an apple, no matter what variety, on the surface you can be pretty sure it’s actually an apple. From there, you can make lots of assumptions about it, like how it will taste when you bite into it and what will happen if you plant the seeds in your yard.

With cancer, we can’t make those kinds of assumptions. While two tumors from the same location in two patients may look the same, doctors and researchers have come to recognize that their behavior and the mutations driving them can be radically different, as can their response to therapy.

With that recognition, physician/scientists like Scott Pomeroy, MD, PhD, the neurologist-in-chief at Boston Children’s Hospital, are taking a deeper look at the tumors they commonly see and asking whether what on the surface looks like one kind of tumor might actually be something completely different. Pomeroy in particular has applied this view to one of the biggest questions in pediatric cancer: Why do medulloblastomas, the most common malignant childhood brain tumor, behave so differently from child to child?

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