Researchers at Kid’s Hospital Los Angeles have received an almost $1 million K08 grant from the National Institutes of Health (NIH)-; in addition to funding from the U.S. Department of Defense-;to support studies into diffuse intrinsic pontine glioma (DIPG), a childhood brain tumor with a 0% survival rate.
The studies -;led by pediatric neurosurgeon Peter Chiarelli, MD, DPhil, and Senior Scientist Meenakshi Upreti, PhD, within the Division of Neurosurgery-; are investigating a novel approach to improve radiation therapy against DIPG, in addition to how one can more specifically goal the cancer from a molecular standpoint.
DIPG tumors are highly aggressive and grow “by invasion,” interlaced with the conventional cells of the critical brainstem. This makes them inconceivable to surgically remove.
Since surgery cannot make a dent on this devastating disease, our lab is combining techniques from materials science, chemistry, molecular biology and genetics to seek out revolutionary ways to treat these tumors.”
Dr. Peter Chiarelli, MD, DPhil, pediatric neurosurgeon
The five-year grant from the NIH National Institute of Neurological Disorders and Stroke will support the team’s studies into using nanoparticles to boost-; and potentially transform-; the effectiveness of radiation therapy.
Radiation therapy is currently the usual of look after DIPG and the one treatment shown to delay survival for these children. But while it might probably shrink tumors temporarily, it isn’t enough to eliminate them.
To enhance these results, Dr. Chiarelli and Dr. Upreti are studying novel nanoparticles-;1,000 times smaller than the common human cell-; in preclinical models of DIPG. The nanoparticles are designed to seek out tumors based on a selected marker the cancer cells have on their surface.
Although nanoparticles have mostly been studied in medicine as a approach to deliver drugs to specific targets, the researchers are taking a novel approach. They’ve developed nanoparticles made up of clusters of various metal atoms at their core, surrounded by a biocompatible polymer shell.
The team is testing different forms of those nanoparticles, in addition to targeting agents, to see in the event that they can successfully deliver functional materials into DIPG tumor cells. The concept is that the targeted materials will enhance the potency and diminish the chance related to standard radiation. The goal is to accentuate therapeutic effects only inside tumor cells-; while guarding normal healthy cells from radiation.
“This might be a paradigm shift in therapy if we could use targeted materials to enable this high-impact radiation to pick just for tumor cells,” Dr. Chiarelli explains. “That might make radiation therapy more powerful but in addition safer at the identical time.”
The team can be focused on understanding the critical microenvironment where DIPG tumors reside. The researchers have developed miniaturized models of the tumors-; called tumor tissue analogs-; that simulate this microenvironment.
“We now have made these tumor tissue analogs in many various formulations,” Dr. Chiarelli says. “What we have found is that they produce a radically different microenvironment than the one which forms from standard tumor cells in a dish. It is a way more realistic model.”
The investigators will ultimately incorporate a 3D microfluidic culture platform that faithfully captures the characteristics of the DIPG microenvironment. This 3D culture system will allow them to observe the expansion of tumors in real-time and see how that microenvironment helps them survive.
Their revolutionary project has recently received support from the Concept Award from the U.S. Department of Defense Rare Cancers Research Program, in addition to from private foundations.
“The concept is to make use of these tumor tissue analogs on this high-throughput platform, where we could screen tons of of various drugs and treatment approaches, all at the identical time,” he explains. “We particularly wish to test newer treatments, comparable to targeted therapies, immunotherapies and viral vector therapies.”
The last word goal for Dr. Chiarelli and Dr. Upreti is to translate their findings into clinical trials for patients in the subsequent five years.
“It is a disease that arises in otherwise healthy children, typically between the ages of 5 and 9,” he says. “It’s devastating to families, and there is an amazing need for brand spanking new therapies and approaches.”
He adds that the lab has benefited from a robust collaboration with senior mentor Rex Moates, PhD, at CHLA. One other key to success? Philanthropic support from families whose children have been treated by Dr. Chiarelli.
“Their generosity has provided vital bridge and seed funding that continues to assist propel our studies to the subsequent level and secure federal funding,” Dr. Chiarelli says. “We’re extremely grateful for his or her support and commitment to improving the lives of kids with this cancer.”
Source:
Kid’s Hospital Los Angeles