Stories about: Dana-Farber Boston Children’s

MATCHing precision medicine to all kids with cancer

Image of human neuroblastoma tumor cells. A new nationwide clinical trial called pediatric MATCH will utilize genomic sequencing to match children with individualized, targeted drugs matched to their tumor profile.
Human neuroblastoma cells.

A multi-center clinical trial is now offering nationwide genetic profiling services to pediatric and young adult cancer patients across the U.S. The goal is to identify gene mutations that can be individually matched with targeted drugs.

“This is the first-ever nationwide precision medicine clinical trial for pediatric cancer,” says pediatric oncologist Katherine Janeway, MD, clinical director of the solid tumor center at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center.

Sponsored by the National Institute of Cancer (NCI) and the Children’s Oncology Group (COG), the so-called NCI-COG Pediatric MATCH trial will screen patients’ tumors for more than 160 gene mutations related to cancer. Nearly 1,000 patients are expected to participate in the trial and it is estimated that 10 percent of those patients will be matched with a targeted therapy.

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Gene therapy halts progression of cerebral adrenoleukodystrophy in clinical trial

David Williams, MD, the principal investigator of the clinical trial, discusses gene therapy and its impact on children with adrenoleukodystrophy

Adrenoleukodystrophy — depicted in the 1992 movie “Lorenzo’s Oil” — is a genetic disease that most severely affects boys. Caused by a defective gene on the X chromosome, it triggers a build-up of fatty acids that damage the protective myelin sheaths of the brain’s neurons, leading to cognitive and motor impairment. The most devastating form of the disease is cerebral adrenoleukodystrophy (CALD), marked by loss of myelin and brain inflammation. Without treatment, CALD ultimately leads to a vegetative state, typically claiming boys’ lives within 10 years of diagnosis.

But now, a breakthrough treatment is offering hope to families affected by adrenoleukodystrophy. A gene therapy treatment effectively stabilized CALD’s progression in 88 percent of patients, according to clinical trial results reported in the New England Journal of Medicine. The study was led by researchers from the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Massachusetts General Hospital.

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“Vampires” may have been real people with this blood disorder

Mural of Vlad the Impaler, who was accused of being a vampire. Perhaps, instead, he suffered from a blood disorder called porphyria.Porphyrias, a group of eight known blood disorders, affect the body’s molecular machinery for making heme, which is a component of the oxygen-transporting protein, hemoglobin. When heme binds with iron, it gives blood its hallmark red color.

The different genetic variations that affect heme production give rise to different clinical presentations of porphyria — including one form that may be responsible for vampire folklore.

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Landmark moment for science as the FDA approves a gene therapy for the first time

Leukemia blast cells, which could now be destroyed using a first-of-its-kind, FDA-approved gene therapy called CAR-T cell therapy
Leukemia blast cells.

Today, the Food and Drug Administration approved a gene therapy known as CAR T-cell therapy that genetically modifies a patient’s own cells to help them combat pediatric acute lymphoblastic leukemia (ALL), the most common childhood cancer. It is the first gene therapy to be approved by the FDA.

“This represents the progression of the field of gene therapy, which has been developing over the last 30 years,” says gene therapy pioneer David A. Williams, MD, who is chief scientific officer of Boston Children’s Hospital and president of the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. “It’s a realization of what we envisioned to be molecular medicine when this research started. The vision — that we could alter cells in a way to cure disease — is now coming true.”

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CRISPR enables cancer immunotherapy drug discovery

Artwork depicting cancer cells with different genes deleted by CRISPR-Cas9, performed to identify novel cancer immunotherapy targets
These cancer cells (colored shapes) each have a different gene deleted through CRISPR-Cas9 technology. In a novel genetic screening approach, the T cells (red) destroy those cancer cells that have lost genes essential for evading immune attack, revealing potential drug targets for enhancing PD-1-checkpoint-based cancer immunotherapy. Credit: Haining Lab 

A novel screening method using CRISPR-Cas9 genome editing technology has revealed new drug targets that could potentially enhance the effectiveness of PD-1 checkpoint inhibitors, a promising new class of cancer immunotherapy.

The method, developed by a team at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, uses CRISPR-Cas9 to systematically delete thousands of tumor genes to test their function in a mouse model. In findings published today by Nature, researchers led by pediatric oncologist W. Nick Haining, BM, BCh report that deletion of one gene, Ptpn2, made tumor cells more susceptible to PD-1 checkpoint inhibitors. Other novel drug targets are likely around the corner.

PD-1 inhibition “releases the brakes” on immune cells, enabling them to locate and destroy cancer cells. But for many patients, it’s not effective enough on its own.

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An unclassified tumor — with a precisely targeted therapy

Jesus (who received targeted therapy for his tumor) pictured with his father
Jesus and his father, Nathaneal

Early last year, at his home in San Juan, Puerto Rico, Jesus Apolinaris Cruz’s leg hurt so much he could barely sleep. “All day,” the 13-year-old recalls. “It was constant pain.” His parents took him to two local pediatricians, who examined him, drew blood, tested his platelets. No diagnosis. Finally, in April 2016, a physician ordered an MRI. No wonder Jesus’s leg hurt. He had a large, cancerous tumor lodged in his hip.

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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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GALLERY: Forecasting the future of pediatric hematology/oncology

Title image for pediatric hematology/oncology predictionsRecently, the annual ASPHO (American Society for Pediatric Hematology/Oncology) meeting brought together more than 1,100 pediatric hematologists and oncologists, including a team from the Dana-Farber/Boston Children’s Cancers and Blood Disorders Center. Some of the delegates from Dana-Farber/Boston Children’s included:

Based on their discussions with their peers, these are their key takeaways from the meeting:

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Naturally-occurring molecule in tree leaves could treat anemia, other iron disorders

Hinoki cypress

“Without iron, life itself wouldn’t be feasible,” says Barry Paw, MD, PhD. “Iron transport is very important because of the role it plays in oxygen transport in blood, in key metabolic processes and in DNA replication.”

Although iron is crucial to many aspects of health, it needs the help of the body’s iron-transporting proteins. Which is why new findings reported in Science could impact a whole slew of iron disorders, ranging from iron-deficiency anemia to iron-overload liver disease. The team has discovered that a small molecule found naturally in Japanese cypress tree leaves, hinokitiol, can transport iron to overcome iron disorders in animals.

The multi-institutional research team is from the University of Illinois, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Brigham and Women’s Hospital and Northeastern University. Paw, co-senior author on the new paper and a physician at Dana-Farber/Boston Children’s, and members of his lab demonstrated that hinokitiol can successfully reverse iron deficiency and iron overload in zebrafish disease models.

“Amazingly, we observed in zebrafish that hinokitiol can bind and transport iron inside or out of cell membranes to where it is needed most,” says Paw.

This gives hinokitiol big therapeutic potential.

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Science then & now: Progress that you can see

Click and drag to compare and contrast archive photos from the lab with current-day images of research at Boston Children’s Hospital.

Then, 1986: Stuart H. Orkin, MD, examines the DNA sequence of a gene.

Now, 2017: Today, Orkin is associate chief of Hematology/Oncology and chairman of Pediatric Oncology at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center (DF/BC). In this photo, he examines a rendering of a gene regulatory molecule’s structure. Orkin’s lab investigates gene regulation of stem cell development, genetic vulnerabilities to cancer and gene and other therapies for treating hemoglobin disorders. 

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