Start Date
2018
Description
Based on genomic data from the Pediatric Precision Genomics Program at Riley Hospital as well as published studies, many recurrent pediatric solid tumors express mutant forms of the tumor suppressor protein p53. p53’s central role in cell cycle arrest and apoptotic pathways has been well studied. Glioblastoma multiforme (GBM) and Ewing’s sarcoma are two cancers with low 5-year survival rates in recurrent pediatric populations. GBM is the most aggressive type of brain tumor, with survival rates that range from 15-30% in pediatrics. Ewing’s is a rare cancer of the bone and the soft tissue around the bones with a 70% survival rate for localized tumors and a 30% survival rate for metastatic tumors. In our laboratory, in vitro and in vivo studies in mutant p53 GBM and Ewing’s sarcoma have demonstrated that the pharmacological inhibition of checkpoint kinase 1 (Chk1) significantly stalls tumor growth, especially when combined with standard-of-care (SOC) DNA-damaging agents. Chk1 is a serine-threonine protein kinase in the DNA-damage response pathway involved in cell cycle arrest. Chk1’s secondary role is to regulate DNA replication forks. To understand the underlying mechanisms of Chk1 inhibition in the context of SOC therapy, we used GBM and Ewing’s sarcoma cell lines to evaluate drug effects on cell cycle arrest and Chk1 activation. These studies will help define biomarkers of therapeutic response that can be used to optimize Chk1-targeted therapies for pediatric GBM and sarcoma
Recommended Citation
Shultz, Jeremiah D.; Bailey, Barbara J.; Pandya, Pankita H.; Ding, Jixin; der Jeught, Kevin Van; Saadatzadeh, M. Reza; Lu, Xiongbin; and Pollok, Karen E., "Chk1 target validation in recurrent mutant p53 pediatric tumors" (2018). Summer Research. 8.
https://digitalcommons.calvin.edu/summer_research/2018/Posters/8
Included in
Chk1 target validation in recurrent mutant p53 pediatric tumors
Based on genomic data from the Pediatric Precision Genomics Program at Riley Hospital as well as published studies, many recurrent pediatric solid tumors express mutant forms of the tumor suppressor protein p53. p53’s central role in cell cycle arrest and apoptotic pathways has been well studied. Glioblastoma multiforme (GBM) and Ewing’s sarcoma are two cancers with low 5-year survival rates in recurrent pediatric populations. GBM is the most aggressive type of brain tumor, with survival rates that range from 15-30% in pediatrics. Ewing’s is a rare cancer of the bone and the soft tissue around the bones with a 70% survival rate for localized tumors and a 30% survival rate for metastatic tumors. In our laboratory, in vitro and in vivo studies in mutant p53 GBM and Ewing’s sarcoma have demonstrated that the pharmacological inhibition of checkpoint kinase 1 (Chk1) significantly stalls tumor growth, especially when combined with standard-of-care (SOC) DNA-damaging agents. Chk1 is a serine-threonine protein kinase in the DNA-damage response pathway involved in cell cycle arrest. Chk1’s secondary role is to regulate DNA replication forks. To understand the underlying mechanisms of Chk1 inhibition in the context of SOC therapy, we used GBM and Ewing’s sarcoma cell lines to evaluate drug effects on cell cycle arrest and Chk1 activation. These studies will help define biomarkers of therapeutic response that can be used to optimize Chk1-targeted therapies for pediatric GBM and sarcoma