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.
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. …
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.
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. …
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. …
“It’s all about the patients,” says Katherine Janeway, MD, when asked about the motivations behind her efforts to bring precision medicine to pediatric oncology. But it’s more than that; the drive to combine science and care is in her blood. A solid tumor specialist and cancer genomics researcher at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Janeway is the sixth generation of her family to choose a scientific or medical path—not just as a career, but also as a form of service.
“Genome” has been the biggest word in cancer research in the last decade. Thanks largely to the high throughput and relatively low cost of “next generation” DNA-sequencing technologies, researchers have screened thousands of tumors for gene mutations that could explain their malignant properties and reveal possible treatment targets.
Sequencing of adult tumors has revealed a broad spectrum of cancer-causing gene mutations. Childhood tumors, by contrast, have turned out to be relatively simple from a genomic point of view. By and large, they harbor few mutations in genes that code for relatively “druggable” targets with discrete effects, like kinases.
Rodriguez-Galindo is not alone in this view. There is a trend afoot in pediatric cancer research: the study of gene regulation and epigenetics is beginning to overshadow classic tumor genetics and genomics. …
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. …
Earlier this month, the American Cancer Society (ACS) released “Cancer Statistics, 2014,” their annual estimate of new cancers diagnoses and deaths for the year ahead. The report was heavily focused on adult malignancies—not surprisingly, given that the number of adult cancer patients in the nation is orders of magnitudes greater than that of childhood patients—but did hold a few insights into childhood cancers.
It showed, for instance, that cancer is still the leading cause of disease-related death among children in the U.S. Leukemias, brain and other nervous system tumors, and sarcomas—tumors of the bones, joints and soft tissues—topped the list of the most lethal cancers for both boys and girls.
Geography can be cruel. An 8-year-old diagnosed with leukemia in Europe or North America can expect a challenging but curable course. Her care, provided by a team of pediatric specialists, includes state-of-the-art imaging, thorough infection prevention and, often, multiple options for treatment.
Her peers in the Middle East and North Africa face a dramatically different prospect. Laboratory and imaging infrastructure can be limited, so diagnoses are made at later, less curable stages. Some patients can’t access acute care because hospital beds are in short supply. Available beds may be occupied by outpatients who can’t return home or palliative patients without access to hospice care. At many hospitals, pediatric inpatients are cramped into 10- to 15-patient wards, raising the risk of infection and other complications for children with compromised immune systems.
The overall lack of medical infrastructure and dearth of providers contribute to a substantial disparity in childhood cancer survival rates between high-income countries and the developing world. While many countries in Europe and North America have achieved cure rates in the 80 percent range, survival rates hover near 20 percent in low- and moderate-income countries. …
The news that your child has cancer always comes as a shock, but for one cancer, acute lymphoblastic leukemia (ALL), parents can take comfort in the fact that doctors are really good at treating it. The cure rate for ALL has, over the last 40 years, climbed to nearly 90 percent.
Less comforting is the fact that some 10 to 20 percent of children who initially respond well to treatment suffer a relapse within five years. And right now, the drugs at our disposal aren’t very good at turning a relapse back into a remission.