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.
About six weeks ago, a glass shattered in my hand, severing the nerve in my pinky finger. The feeling in my fingertip still hasn’t returned, and now I know why: I’m too old.
Going back to World War II, it’s been speculated that recovery of peripheral nerve injuries—like those in limbs and extremities—is influenced by age. And studies indicate that peripheral neuropathy is common in people over 65, including those who have received cancer chemotherapy, and often unexplained.
“When you’re very young, the system is very plastic and able to regenerate,” Michio Painter told me recently. He is a graduate student in the laboratory of Clifford Woolf, PhD, director of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital. “After that, there’s a gradual decline. By the age of 30, much of this plasticity is gone.”
Traditionally, this decline has been thought to reflect age-related differences in neurons’ ability to regrow, but when Painter studied neurons in a dish, he couldn’t confirm this.
Drugs like cisplatin that break DNA are some of the strongest weapons we have against breast, ovarian and other cancers. The problem, common to every form of chemotherapy, is that cisplatin doesn’t work for everyone. Given the potential side effects that go along with the drug—including vomiting, hearing loss and muscle cramps, just to name a few—the decision to give it to a patient becomes something of a gamble: Does the benefit outweigh the risk?
There are tests that examine individual genes and which can give doctors a limited view as to which tumors might respond best to cisplatin. But a multicenter team co-led by Zoltan Szallasi, MD, of Boston Children’s Hospital’s Informatics Program (CHIP), thinks they may have a solution that looks beyond individual genes to see which tumors might succumb to cisplatin and other drugs like it.
If there’s anything that tumors are good at, it’s hiding themselves. Not from things like MRIs or CT scans, mind you, but from the immune system. Since a tumor grows from what were at one time normal, healthy cells it’s still “self,” still one of the tissues that makes you you.
Researchers have worked for years on cancer vaccines aimed at getting the immune system to wake up to the presence of a tumor and turn on it. With a Phase 1 safety trial , Kieran and his colleagues, including Children’s neurosurgical oncologist Lily Goumnerova, are evaluating a different strategy for patients with hard-to-treat brain tumors called malignant gliomas: They’re giving the tumors a cold.
Some scientists still debate the existence of cancer stem cells – rare cells that can singlehandedly perpetuate a tumor, and possibly make it more aggressive. But others have moved on, isolating candidate cancer stem cells and documenting their distinctive characteristics and markers.
And some are starting to figure out how these cells operate and leverage that knowledge to come up with new approaches to cancer therapy.
Children’s scientist Markus Frank has been building quite a dossier on cancer stem cells, starting with melanoma stem cells. “Many of the features that make a cancer bad seem to be localized in this subpopulation of cells,” he says.
Before Children’s Hospital Boston’s own Frances Jensen, Director of Epilepsy Research, took the stage yesterday, Richard Saul Wurman, organizer of TEDMED and the TED conferences, spoke warmly of Children’s participation and sponsorship of this year’s event. A generous gift from the Hassenfeld Family Initiatives enabled that participation, and Wurman thanked the Hassenfelds and Children’s for bringing “such interesting people” to TEDMED 2010. With that, Jensen began her talk about the importance of understanding the developing brain.