Targeting Angiogenesis for Controlling Neuroblastoma

Subhasree Roy Choudhury,Naren L Banik,Surajit Karmakar,Swapan K Ray

doi:10.1155/2012/782020

Subhasree Roy Choudhury, Naren L Banik + Show 2 more

Open Access

https://doi.org/10.1155/2012/782020

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Abstract

Neuroblastoma, a progressive solid tumor in childhood, continues to be a clinical challenge. It is highly vascular, heterogeneous, and extracranial tumor that originates from neural crest. Angiogenesis, genetic abnormalities, and oncogene amplification are mainly responsible for malignant phenotype of this tumor. Survivability of malignant neuroblastoma patients remains poor despite the use of traditional therapeutic strategies. Angiogenesis is a very common and necessary pre-requisite for tumor progression and metastasis. Angiogenesis is also a major factor in making malignant neuroblastoma. Thus, prevention of angiogenesis can be a highly significant strategy in the treatment of malignant neuroblastoma. Here, we summarize our current understanding of angiogenesis in malignant neuroblstoma and describe the use of experimental anti-angiogenic agents either alone or in combination therapy. This review will clearly indicate the importance of angiogenesis in the pathogenesis of malignant neuroblastoma, its prevention as a promising therapy in preclinical models of malignant neuroblastoma, and prospective clinical trials.

Highlights

Neuroblastoma is the most common, extracranial, and heterogeneous solid tumor in children, and it accounts for approximately 15% of pediatric cancer deaths with an estimated incidence of 1 per 7000 births in the USA [1, 2]
Despite aggressive conventional treatments and diagnosis techniques in neurosurgery, the survival rate for patients with neuroblastoma remains poor because the majority of children older than 1 year of age with advanced stage neuroblastoma die from progressive disease and only 40% of children over 4 years old with neuroblastoma survive for 5 years, emphasizing the urgent need for the development of innovative therapeutic strategies for treatment of malignant neuroblastoma
Angiogenesis is a process of development of intrinsic vascular network, and it is a prerequisite for progression and metastatic spread of solid tumors like neuroblastoma where new capillaries sprout from preexisting vessels and the transition from avascular to vascular phase occurs via neovascularization

Summary

Introduction

Neuroblastoma is the most common, extracranial, and heterogeneous solid tumor in children, and it accounts for approximately 15% of pediatric cancer deaths with an estimated incidence of 1 per 7000 births in the USA [1, 2]. This embryonal cancer of postganglionic sympathetic nervous system arises from adrenal gland and less frequently metastasizes in other places such as chest, neck, lymph nodes, pelvis, liver, and bone. Neuroblastoma is characterized by its intriguing clinical behaviors that include spontaneous differentiation and regression, maturation into benign ganglioneuroma, and deadly metastatic tumor. Inhibitors are expected to improve patient survivability by reducing morbidity, mortality, and drug-related toxicity

Angiogenesis in Human Neuroblastoma

Angiogenic Growth Factors and Their Implications

Single Anti-Angiogenic Agent Therapy for Controlling Neuroblastoma

Findings

Conclusion and Future Direction