Stories about: Ewing sarcoma

ctDNA: Bringing ‘liquid biopsies’ to pediatric solid tumors

Brian Crompton studies the use of ctDNA as an alternative way to biopsy pediatric solid tumors
Brian Crompton with Stephanie Meyer (left) and Kellsey Wuerthele (PHOTO: JOHN DEPUTY)

Our blood carries tiny amounts of DNA from broken-up cells. If we have cancer, some of that DNA comes from tumor cells. Studies performed with adult cancers have shown that this circulating tumor DNA (ctDNA) may offer crucial clues about tumor genetic mutations and how tumors respond to treatment.

Brian Crompton, MD, with colleagues at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and elsewhere, is now working to bring ctDNA “liquid biopsies” to pediatric solid tumors as well. The researchers hope that these blood tests will eventually improve early detection, choice of treatment and monitoring of young patients with these diseases without having to sample the tumor itself.

Read Full Story | Leave a Comment

Cancer researchers hit a bullseye with a new drug target for Ewing sarcoma

Cell staining shows the lethal efficacy of CDK+PARP inhibitors against Ewing sarcoma
Fluorescent staining shows how PARP and CDK12 inhibitors combine to deal a lethal blow to Ewing sarcoma. In the top row, green represents locations of DNA damage incurred by Ewing sarcoma cells. In the bottom row, red represents DNA repair activity. Together, PARP and CDK12 inhibitors lead to Ewing sarcoma cell death.

Screening a class of recently-developed drug compounds — so-called “CDK inhibitors” capable of blocking CDK7/12/13 proteins — against hundreds of different human cancer cell lines, researchers at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center have found that CDK12 inhibitors pack a particularly lethal punch to Ewing sarcoma, a rare cancer typically affecting children and young adults.

“No one has previously considered CDK12 inhibition as a way to combat Ewing sarcoma,” says Kimberly Stegmaier, MD, senior author of the new Cancer Cell paper that describes the findings.

In 2014, Nathaneal Gray, PhD, co-author on the new paper, and his team were the first to develop CDK inhibitors.

Some individuals were entirely cured of the disease

“Now, in mice, we’ve shown that Ewing sarcoma cells die if CDK12 is knocked out genetically or chemically inhibited,” Stegmaier says. What’s more, her team has discovered that CDK12 inhibition can be combined with another drug, called a PARP inhibitor, to double down on Ewing sarcoma cells.

The revelation that CDK12 inhibition can kill Ewing sarcoma cells brings a surge of hope to the field of pediatric oncology, which has long been challenged to find new drugs against childhood cancers.

Read Full Story | Leave a Comment

Targeting noncoding RNAs could be game-changing in childhood cancer: Triche

The war on pediatric cancer hasn’t been going so well in the past couple of decades, says Timothy Triche, MD, PhD, a cancer researcher at Children’s Hospital Los Angeles. The existing intensive chemotherapy regimens carry a lot of “unfortunate baggage” for children in terms of lifelong morbidity, and haven’t brought about a tremendous change in outcomes, he says.

“We really don’t have a lot of new drugs, if any, and we really don’t have new targets,” he said at Boston Children’s Hospital’s Global Pediatric Innovation Summit + Awards last month. “Underlying this is the fundamental problem that we don’t understand a lot more about childhood cancer than we did before.”

In a Discovery Roundup highlighting four big ideas in pediatric care, Triche made the case for targeting the genome’s “dark matter” — the vast number of RNAs made from the genome that do not code for proteins.

Read Full Story | Leave a Comment

Why we need more research into childhood cancer

WilliamsDavidDSC_0056PreviewlargeDavid A. Williams, MD, is chief of hematology/oncology at Boston Children’s Hospital and associate chairman of pediatric oncology at Dana-Farber Cancer Institute. This column was first published on Huffington Post.

The fact that childhood cancer is, thankfully, rare belies the fact that it is the leading cause of disease-related death in U.S. children age 1 to 19. The number of people with a direct stake in expanding research into pediatric cancer is quite large, well beyond the small number of children with cancer and their families. Not only are the life-long contributions of children cured of cancer enormous, but understanding cancers of young children could also hold the key to understanding a broad range of adult cancers. The time is ripe to allocate more resources, public and private, to research on pediatric cancer.

In an age of increased understanding of the genetic basis of diseases, one thing is striking about many childhood cancers. They are relatively “quiet” cancers, with very few mutations of the DNA. Young children haven’t lived long enough to acquire the large number of mutations that create the background “noise” associated with years of living. This makes it much easier to pinpoint the relevant genetic abnormalities in a young child’s cancer.

Add to this the growing realization that biology, including how various tumors use common “pathways,” is a major factor in how the cancer responds to treatment. Thus, a mechanism that’s relatively easier to observe in the cancers of young children could help scientists understand cancers in adults, in whom the same mechanism is hidden amid the clutter of mutations acquired over a longer life.

Read Full Story | Leave a Comment