Abstract
Neuroblastoma is a pediatric cancer that arises from neural crest cells failing to differentiate into mature neuronal cells. Differentiation therapy is one of the effective approaches to treat high-risk neuroblastoma. Developing new differentiation agents that can be used to treat neuroblastoma, especially for those resistant to currently available differentiation agents, is a major task in the field of neuroblastoma research. It has been known that neuroblastoma cell differentiation is tightly coupled with cell cycle progression. More importantly, multiple cell cycle regulating proteins have been shown to play critical roles in modulating neuroblastoma differentiation process, suggesting the potential of targeting these cell cycle regulators for differentiation therapy. Here we review the cell cycle regulators that have been recognized to function as independent regulators of cell differentiation, including cyclindependent kinase 4, cyclin D1, and the Cip/Kip family proteins, with a focus on their involvement of the differentiation of neuroblastoma cells. We also discuss the potential and approaches of discovering new cell cycle-regulating differentiation agents from common sources of anti-cancer agents such as extracts from plants.
Highlights
Neuroblastoma is a spectrum of pediatric neuroblastic tumors that affects more than 700 children in the United States per year [1, 2]
We review recent advances in understanding the role of cell cycle regulators in cell differentiation with a primary focus on regulators that have been studied in neuroblastoma cell differentiation, and discuss the potential of targeting cell cycle progression for differentiation therapy in neuroblastoma
The molecular mechanisms by which the cell cycle regulators direct the cell differentiation process are not fully understood, the findings suggest that targeting these cell cycle regulators is an effective approach to differentiation therapy
Summary
Neuroblastoma is a spectrum of pediatric neuroblastic tumors that affects more than 700 children in the United States per year [1, 2]. It is a type of solid tumor cancer that arises from neural crest cells of the sympathetic nervous system that fail to differentiate into mature neurons [3]. We review recent advances in understanding the role of cell cycle regulators in cell differentiation with a primary focus on regulators that have been studied in neuroblastoma cell differentiation, and discuss the potential of targeting cell cycle progression for differentiation therapy in neuroblastoma
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