Advances and Answers in Pediatric Health
Vemurafinib + Chloroquine
H3K27M. It is a mutation to credence to the potential a histone, and histones are of this approach. The two how we package our DNA. … institutions have since joined [ The different ways ] histones forces to share data and are modified, gives code to work with pharmaceutical say,‘ Transcribe here, don’ t companies to advance the transcribe here.’ And DIPGs research and potentially alter that dramatically,” Dr. make a significant impact for Dahl explains.“ Being able to children with the disease. find a protein that is involved in the transcription that occurs
As a result, Dr. Dahl expects as a consequence of that, was a that he’ ll be able to begin really unique way of targeting offering zotiraciclib, which that underlying mutation.” is currently in clinical trials for use in adults, to pediatric
With that in mind, Dr. patients in about a year.
Dahl examined existing pharmaceutical compounds
“ What’ s really exciting to that target CDK9 to identify us is it’ s not a variation on ones that might be effective in something that has been entering the brain and treating tried. It’ s coming at it with
DIPG. He ultimately landed on a different approach. Will a drug called zotiraciclib. At it work? I don’ t know, … but the same time, researchers at I think that we have a lot of
UPMC Children’ s Hospital of really exciting data that we’ ve
Pittsburgh arrived at the exact shown, and this at least has the same drug, lending further potential to bring something new to the field that nobody’ s tried before,” he says.“ And I think the impact to me is that we have a new drug that we’ re going to be able to offer families in a field that’ s desperately in search of new ideas.”
A‘ SMART’ APPROACH TO DIPG
Dr. Dahl is also collaborating with Dr. Venkataraman to address a major barrier in DIPG treatment: radiation resistance. In studying how DIPG cells become resistant to radiation, the team discovered a gene that protects tumor cells. Drs. Venkataraman and Dahl got to work searching for a drug designed to inhibit that gene and found one: venetoclax. That drug is already FDA-approved, which quickened the process of moving it into clinical trials for kids.
Dr. Venkataraman’ s work extends beyond improving current radiation treatments to finding entirely new solutions, as well. One of the major challenges to treating DIPG tumors is their location in the pons. In order to reach the tumor, a drug must be able to cross the blood-brain barrier— a selective semipermeable wall of cells that keeps harmful substances from affecting the brain. This barrier has rendered chemotherapy useless against DIPG.
To overcome this challenge, Dr. Venkataraman turned to one of the few cells that can cross the blood-brain barrier: CAR T-cells. But used unaltered, CAR T-cells would target not just cancer cells, but healthy cells. This prompted her to engineer something she’ s calling“ smart CARs” in collaboration with M. Eric Kohler, MD, PhD. Dr. Venkataraman identified two antigens that are highly expressed on DIPG tumor cells and that aren’ t found together on healthy cells.
“ We engineered the T-cells in such a way that if both the antigens are present, they target and kill the cells, but if only one is present, they just leave them alone. The CAR T-cells faithfully follow that,” she explains.“ We tested it in animal models and found that where it cleared the tumor, it did not do anything to the normal cells.”
What’ s more, the study found that the smart CARs persisted in the body for long periods of time, meaning that should the tumor recur, the specially engineered CAR T-cells could go right to work, killing the tumor cells immediately.
This research, and that of her colleagues Dr. Dahl and Dr. Mulcahy Levy( with whom she works on glioma research), is providing an entirely new avenue for treating some of the most devastating tumors that exist. And for Dr. Venkataraman, who lost her own son to cancer, that potential impact is invaluable. •
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