University of Dundee

"Childhood cancer epigenetic drug development and clinical trials"

Event Date: 
Thursday, February 3, 2022 - 10:00 to 11:00
Event Location: 
Teams
Host: 
Professor Alessio Ciulli FRSC
Event Speaker: 
Dr Charles Keller,
Institution: 
Scientific Director and Chief Mission Officer, Children’s Cancer Therapy Development Institute, Oregon, USA
Event Type: 
Seminar
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Abstract:

This presentation on the childhood solid tumor rhabdomyosarcoma will share sentinel findings from our laboratory including the first demonstration that many translocation-mediated oncogenes are not expressed at a constant level, but are expressed in a cell-cycle phase specific manner (G2 in the case of Pax3:Foxo1).  We have also established that tumor-initiating mutations such as Pax3:Foxo1 are dispensable for tumor maintenance, but critically important for treatment resistance and tumor evolution through a process called checkpoint adaptation, which is borrowed by cancer cells from yeast.  And although it might have seemed improbable at the onset, the cell-of-origin studies conducted by our laboratory have been the most informative in the development of potential new therapies for sarcomas.  Specifically, the publications below have resulted in 3 clinical trial concepts and trials for adults and children with rhabdomyosarcoma and the recently completed pediatric phase I trial for entinostat [NCT02780804/ADVL1513, a phase II trial for rhabdomyosarcoma now under consideration, and European study NCT03838042].  Clinical trial approaches take into account the understanding that the SWI-SNF chromatin remodeling complex motor SMARCA4 is required short-term to control Pax3:Foxo1 oncogene-mediated chemotherapy resistance, but that SMARCA4 is required for tumor cell maintenance long-term.  

Biography:

Charles’ research focuses on the development of more effective, less toxic therapies for childhood cancers. His special interest is advanced disease that has spread beyond the initial location of the cancer or which makes the tumor unresectable. Charles has co-chaired the brain tumor developmental therapeutics committee (CNS-DVL) of the Children’s Oncology Group and is a member of the soft tissue sarcoma (STS) committee of Children’s Oncology Group. He has also regularly been a standing or ad hoc member of NIH/NCI Study Sections.

Charles attended Tulane University where he received a degree in Biomedical Engineering prior to attending Baylor College of Medicine where he received his M.D. degree. After completing his internship and residency in Pediatrics at Texas Children’s Hospital, Charles trained in Pediatric Hematology-Oncology at the University of Utah and with 2007 Nobel laureate, Mario Capecchi. Charles has authored over 140 scientific publications and is a recognized expert in the biology of childhood sarcomas and the preclinical investigation of childhood cancers. Charles is also a co-founder of Artisan Biopharma (a company helping translate drug discoveries to clinical use) and Tio Companies that improves drug safety and cancer drug effectiveness*. In their spare time, Charles and his daughters enjoy outdoor adventures, as well as designing and building treehouses and Japanese Teahouses.

All Welcome

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