Stories about: cancer

A metabolic treatment for pancreatic cancer?

nitrogen disposal is important to pancreatic cancer
Targeting an enzyme that helps dispose of excess nitrogen curbed malignant growth of pancreatic tumors in obese mice.

Pancreatic cancer has become the third leading cause of cancer mortality. Its incidence is rising in parallel with the rise in obesity, and it’s hard to treat: five-year survival still hovers at just 8 to 9 percent. A new study published online in Nature Communications finds early success with a completely new, metabolic approach: reducing tumors’ ability to get rid of excess nitrogen.

The researchers, led by Nada Kalaany, PhD, of Boston Children’s Hospital’s Division of Endocrinology and the Broad Institute of MIT and Harvard, provide evidence that targeting the enzyme arginase 2 (ARG2) can curb pancreatic tumor growth, especially in people who are obese.

“We found that highly malignant pancreatic tumors are very dependent on the nitrogen metabolism pathway,” says Kalaany.

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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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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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Angiogenesis: The slow growth of a science

angiogenesis

Sometimes a scientific idea takes a long time to make its way forward. Angiogenesis is a case in point. As surgeon-in-chief at Boston Children’s Hospital, Judah Folkman, MD, noted that malignant tumors often had a bloody appearance. In The New England Journal of Medicine in 1971, he hypothesized that tumors cannot grow beyond a certain size without a dedicated blood supply, and that “successful” tumors secrete an unknown substance that encourages blood vessel growth, or angiogenesis.

If angiogenesis could be blocked, he argued, tumors might not grow or spread. Rather than waging a toxic chemical and radiation battle with a tumor, one could starve it into submission by shutting down its blood supply.

The idea was roundly criticized.

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Do children with Down syndrome need modified chemo for leukemia? No, says study

leukemia down syndrome acute lymphoblastic leukemia

Clinicians have long known that children with Down syndrome carry an elevated risk of developing acute lymphoblastic leukemia (ALL), the most common pediatric cancer. Research consistently shows that children with Down syndrome are more likely to suffer complications from chemotherapy. At the same time, some studies have suggested that children with Down syndrome and ALL may have a higher chance of relapsing.

What to do with this knowledge has been a source of controversy. Should patients with ALL and Down syndrome receive treatment modified to minimize toxicity from chemotherapy? Or should they be given the same treatment as other children with ALL to minimize the chance for relapse? Recent study results from Dana-Farber/Boston Children’s Cancer and Blood Disorders Center suggest that full-dose chemo is preferable.

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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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Rainbow-hued blood stem cells shed new light on cancer, blood disorders

color-coded blood stem cells
These red blood cells bear color tags made from random combinations of red, green and blue fluorescent proteins. Same-color cells originate from the same blood stem cell (Nature Cell Biology 2016, Henninger et al).

A new color-coding tool is enabling scientists to better track live blood stem cells over time, a key part of understanding how blood disorders and cancers like leukemia arise, report researchers in Boston Children’s Hospital’s Stem Cell Research Program.

In Nature Cell Biology today, they describe the use of their tool in zebrafish to track blood stem cells the fish are born with, the clones (copies) these cells make of themselves and the types of specialized blood cells they give rise to (red cells, white cells and platelets). Leonard Zon, MD, director of the Stem Cell Research Program and a senior author on the paper, believes the tool has many implications for hematology and cancer medicine since zebrafish are surprisingly similar to humans genetically.

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Treating relapsed child leukemia by matching therapy to the mutations

next generation sequencing cancer drugs child leukemia
(Bainscou / National Cancer Institute / Wikimedia Commons)

Although current treatments can cure 80 to 90 percent of cases, acute lymphoblastic leukemia (ALL) remains the second leading cause of cancer deaths in children. Patients with a resistant form of the disease, who relapse following successful treatment or who have other high risk features have few treatment options. Acute myeloid leukemia (AML) is also difficult to treat in children.

In a first-of-its-kind study, investigators at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center are testing precision cancer medicine in children and young adults with relapsed or high-risk leukemias. The goal is to determine whether powerful next-generation DNA sequencing can spot mutations or genetic changes in leukemia cells that can be targeted by cancer drugs.

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