Although there are more than 150 types of childhood cancer, pediatric cancer receives only a small fraction of NIH and National Cancer Institute funding, Williams writes. Yet, he points out, just as breakthroughs in adult cancer research can help children, breakthroughs in pediatric cancer can also benefit adults.
Williams and other members of the Coalition for Pediatric Medical Research recently met with the staff of Vice President Joseph Biden, leader of the federal government’s cancer moonshot. Their message? Make sure that pediatric cancer is represented on the moonshot.
An occasional roundup of news items Vector finds noteworthy.
Zika’s surface in stunning detail; mosquito tactics
We haven’t curbed the Zika epidemic yet. But cryo-electron microscopy — a newer, faster alternative to X-ray crystallography — at least reveals the structure of the virus, which has been linked to microcephaly (though not yet definitively). The anatomy of the virus’s projections gives clues to how the virus is able to attach to and infect cells, and could provide toeholds for developing antiviral treatments and vaccines. Read coverage in the Washington Post and see the full paper in Science.
Meanwhile, as The New York Times reports, scientists are coming together in an effort to control Zika by genetically manipulating the mosquito that spreads it, Aedes aegypti. …
Programmed cell death, or apoptosis, helps keep us healthy by ensuring that excess or potentially dangerous cells self-destruct. One way cells know it’s time to die is through signals received by so-called death receptors that stud cells’ surfaces. When these signals go awry, the result can be cancer (uncontrolled cell growth) or autoimmune disease (cells self-destructing too readily).
Researchers at Harvard Medical School (HMS) and the Program in Cellular and Molecular Medicine at Boston Children’s Hospital deconstructed a death receptor called Fas to learn more about its workings, using nuclear magnetic resonance (NMR) spectroscopy to reveal its structure.
They found that for immune cells to hear the “time to die” signal, a portion of Fas called the transmembrane region must coil into an intricate three-part formation, allowing the signal to pass into the cell. The NMR imaging also revealed that the amino acid proline is critical for the formation’s stability. Cancer-causing mutations in the transmembrane region (one of them affecting proline itself) deformed this delicate structure and prevented signals from passing through.
This better understanding of the Fas death receptor, published last week in Molecular Cell, could lead to new approaches that bypass Fas to encourage apoptosis in cancer or, conversely, inhibit Fas in autoimmune disease.
Oral squamous cell carcinoma (OSCC), a kind of oral cancer, affects some 30,000 Americans annually. It spreads through the lymphatic system and often has already metastasized by the time it’s diagnosed. The top image here, from a recent study in the American Journal of Pathology, is a healthy mouse tongue; the bottom is the swollen tongue of a mouse with OSCC. The cancerous tongue is overloaded with lymphatic vessels, appearing in blue and white, which help the tumor spread to the regional lymph nodes. The Bielenberg lab in Boston Children’s Hospital’s Vascular Biology Program is studying ways of blocking the progression of this and other cancers by inhibiting their spread through the lymphatic system. (Image: Bielenberg laboratory/Kristin Johnson)
It’s long been a mystery why some of our cells can have mutations associated with cancer, yet are not truly cancerous. Now researchers have, for the first time, watched a cancer spread from a single cell in a live animal, and found a critical step that turns a merely cancer-prone cell into a malignant one.
Their work, published today in Science, offers up a new set of therapeutic targets and could even help revive a theory first floated in the 1950s known as “field cancerization.”
“We found that the beginning of cancer occurs after activation of an oncogene or loss of a tumor suppressor, and involves a change that takes a single cell back to a stem cell state,” says Charles Kaufman, MD, PhD, a postdoctoral fellow in the Zon Laboratory at Boston Children’s Hospital and the paper’s first author. …
More than 75 percent of children diagnosed with cancer are surviving into adulthood, leaving more and more parents to wonder: Will my child be able to have children down the road?
They’re right to be concerned. The cancer treatments that are so effective at saving children’s lives can themselves cause a host of problems that don’t manifest until years later. These late effects include particularly harsh impacts on fertility.
On our sister blog Notes, urologist Richard Yu, MD, PhD, of Boston Children’s Hospital and fertility specialist Elizabeth Ginsberg, MD, of Brigham and Women’s Hospital outline where the science of fertility preservation is going.
“It may take 15 or 20 years to develop the techniques to help a child who is 8 years old now,” notes Yu. “But if you don’t preserve something now, you run the risk of not being able to do anything for them later, which is where we are now with a large number of adults who survived childhood cancer.”
We’ve all heard the George Santayana quote, “Those who cannot remember the past are condemned to repeat it.” But there’s another way of thinking about the lessons that the past holds for the future: Those who do remember the past can recapture and harness earlier feelings of energy, urgency and possibility to overcome new problems, now and in the future.
In taking the audience on a tour through the last 60 years of advances in cancer biology, genomics and treatment, Mukherjee highlighted the central role pediatrics played as the starting point for the cancer successes we see today. How, he asked, did children come to play such a central role? What can we learn from the successes in the 1950s and ’60s, when pediatric cancer started to evolve from a death sentence to a treatable, even curable disease?
And how, he asked, can we recapture and harness the energy and urgency of that time today?
The 20th century saw great strides in curing childhood cancer, thanks primarily to the discovery that broadly toxic chemotherapy agents could kill malignant cells. Once virtually incurable, pediatric cancer now has an overall long-term survival rate topping 80 percent.
Recent clinical trials for patients with advanced melanoma have found that a new class of drugs—anti-PD-1 antibodies—can elicit an unprecedented response rate. In the last year, the FDA gave accelerated approval to two anti-PD-1 antibodies, nivolumab and pembrolizumab, for patients with advanced melanoma (including Jimmy Carter) who are no longer responding to other drugs. And there’s growing evidence that this class of drugs may be effective in treating other forms of cancer.
Anti-PD-1 antibodies target a receptor on activated T cells, known as the programmed cell death 1 (PD-1) receptor. Tumor cells stimulate this inhibitory receptor to dodge immune attack, whereas anti-PD-1 antibodies block the same pathway, “waking up” the immune cells so they can attack the cancer. The drugs have been hailed as one of the first cancer immunotherapy success stories. …
Growing up in the San Francisco area, Cigall Kadoch, PhD, had a passion for puzzles. The daughter of a Moroccan-born, Israeli-raised father and a mother from Michigan who together developed an interior design business, Kadoch excelled in school and pretty much everything else. Above all, she loved to solve brain-teasers.
In high school, however, Kadoch came up against a problem that defied solution. Breast cancer took the life of a beloved family caretaker who had nurtured her interests in science and nature. She knew little about cancer except that it took lives far too early.
“I was deeply saddened and very frustrated at my lack of understanding of what had happened,” recalls Kadoch. “I thought to myself, cancer is a puzzle that isn’t solved, let alone even well-defined, and I want to try. As naïve a statement as that was, it was a defining moment—one which I never could have predicted would actually shape my life’s efforts.” …