A new research study from the CBTP lab entitled “Combined Targeting of PI3K and MEK Effector Pathways via CED for DIPG Therapy,” was published in Neuro-Oncology Advances on May 29, 2019. The published manuscript, submitted by Dr. Uday Maachani (Dr. Souweidane Lab) on behalf of the entire research team, showed the results of a comprehensive study of midline gliomas including diffuse intrinsic pontine gliomas (DIPG), and the relationship between amplified phosphatydylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MEK), and the development of these particular tumor types.
In this comprehensive study, the research team tested both PI3K inhibitor ZSTK474 and MEK inhibitor trametinib, alone and in combination in vitro and in vivo, using various delivery methods.
The results showed that combination treatments were found to be synergistic with dosing across the cell lines tested, and significant tumor suppression was seen when given systemically against a subcutaneous DIPG model, and when given via convection-enhanced delivery (CED) in an intracranial DIPG mouse model. Data indicates that ZSTK474 and trametinib combination therapy inhibits malignant growth of DIPG cells in culture and in animal models, prolonging survival. The results warrant further investigation and the team is excited by the potential for a promising new combination approach to treat DIPG via CED.
Funding: This research was supported in part by Cristian Rivera Foundation, McKenna Claire Foundation, The Lyonhearted Foundation, Christian Koehler Foundation, Brooke Healey Foundation, Fly a Kite Foundation, Children’s Brain Tumor Family Foundation, Joshua’s Wish, Lily LaRue Foundation, and by the Alex Lemonade Stand Foundation’s Pediatric Oncology Student Training Grant (UT), and American Brain Tumor Association Medical Student Summer Fellowship in honor of Collegiate Charities Dropping the Puck on Cancer and Super Lucy (RC).
On behalf of Dr. Mark Souweidane and the Children’s Brain Tumor Project, we are proud to announce that the Lancet Oncology has published the highly anticipated results of Dr. Mark Souweidane’s first-ever dose escalation study using convection-enhanced delivery (CED) in patients with diffuse intrinsic pontine glioma (DIPG). The milestone Phase I clinical trial, which investigated the safety of using CED to bypass the blood-brain barrier and administer a drug directly to a brain stem tumor site, resulted in no serious adverse effects and no dose-limiting toxicity; researchers conclude that the technique is safe to use in children.
This publication validates a career-long hypothesis that Dr. Souweidane put forth more than 20 years ago, and was only made possible by the families who entrusted their children in his care by enrolling in the trial, and the donors who have provided the financial support to enable this research (read his inspiring blog here).
The results are so promising, they are expected to eventually change the landscape of future pediatric brain tumor protocols.
Dr. Jeffrey Greenfield, Co-Founder of the Children’s Brain Tumor Project, has accepted an invitation to become a standing member of the Weill Cornell Medicine Englander Institute for Precision Medicine. Dr. Greenfield’s formal affiliation with the Institute is in recognition of his work in genomic sequencing of pediatric brain tumors and his ongoing research collaboration with the Institute.
The St. Baldrick’s Foundation, the largest private funder of childhood cancer research grants, has just announced its newest round of grants, and Weill Cornell’s Children’s Brain Tumor Project is proud to be a recipient. St. Baldrick’s has committed to grant more than $2 million to support the next generation of St. Baldrick’s Fellows and Summer Fellows at 27 institutions across the U.S.
The Children’s Brain Tumor Project is a leader in leveraging precision medicine to help inform customized treatment protocols for children with brain tumors. As a result, Dr. Jeffrey Greenfield’s lab team was invited to present at the 2nd Pediatric Precision Oncology Conference.
Building on the success of last year’s “Summer Sprint,” the Children’s Brain Tumor Project has initiated several new projects that take advantage of summer grants as well as the additional resources we now have available through Dr. Dahmane’s laboratory. Read more
These are exciting times in pediatric neuro-oncology research, and nowhere is that excitement felt more than right here in the CBTP labs. We have recently doubled in size, thanks to the generous support of our families and friends. Where once our two teams worked side by side, taking parallel paths toward our common goal, now we are four. And we couldn’t be happier about that. Read more
Dr. Michael Kaplitt, our Vice Chair for Research, made news this summer when he became the first in New York to use Magnetic Resonance-guided Focused Ultrasound (MRgFUS) to treat patients with essential tremor, just a week after the technology received FDA approval. The completely non-invasive technique uses 1,000 low-energy ultrasound waves focused on a precise spot in the brain, each individual wave sparing healthy tissue while the combined energy destroys its target. Read more
Perhaps the greatest milestone in 2016 came when Dr. Uday Bhanu Maachani established two gliomatosis cerebri cell cultures from living patients. From one of these lines he created a xenograft: A mouse model with a GC tumor sampled from an actual patient. This is the only animal model anywhere in the world with a GC tumor cultured from a patient. Read more