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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