Children with aggressive neuroblastoma have low survival rates due to frequent recurrences and treatment resistance. A better understanding of the ways neuroblastoma tumors develop resistance to therapy will provide improved treatment options for these children. Growth factor receptors are proteins on tumor cells that can promote tumor cell survival, growth and spread, and the amounts of growth factor receptors found on neuroblastoma tumor cells can be associated with chemotherapy resistance. However, the ways in which tumor cells control the levels and activity of growth factor receptors are not understood.
Some tumor cells have been shown to control the levels of growth factor receptors through recycling of “used” receptors back to the tumor cell surface. Recently a collaborative group including investigators from Texas Children’s Hospital demonstrated that UBE4B, a protein whose gene is often lost in neuroblastoma tumors, interacts with other proteins responsible for control of growth factor receptor recycling within tumor cells, suggesting a connection between growth factor receptor recycling and neuroblastoma tumor response to treatment.
The investigators demonstrated that the amount of the UBE4B gene that is expressed in neuroblastoma tumors directly correlates with the chances of patients surviving, with low gene expression associated with lower chances of survival. The investigators also demonstrated that UBE4B levels are associated with the levels of the epidermal growth factor receptor (EGFR), and that the function of UBE4B could affect the responses of neuroblastoma tumors to EGFR inhibitory drugs (Zage and Bean 2012; Zage et al 2013).
The exciting results of this and other research projects at Texas Children’s Hospital will help identify better treatments and identify new targets for future drug development for children with neuroblastoma. New treatment strategies are currently undergoing testing at Texas Children’s Hospital and future research by the scientists in the neuroblastoma program at Texas Children’s Hospital will continue to explore new pathways, new targets, and new treatments in order to provide the most appropriate and most effective therapy for each and every child with neuroblastoma.
Zage P.E.*, N. Sirisaengtaksin*, Y. Liu, M. Gireud, B.S. Brown, S. Palla, K.N. Richards, D.P.M. Hughes, and A.J. Bean. UBE4B Levels Are Correlated with Clinical Outcomes in Neuroblastoma Patients and with Altered Neuroblastoma Cell Proliferation and Sensitivity to EGFR Inhibitors. Cancer. In Press. PMID: 22990745
Zage, P.E. and A.J. Bean. 2012. Growth Factor Receptor Trafficking as a Potential Therapeutic Target in Pediatric Cancer. Frontiers in Biology. 7 (1): 1-13.