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Forum on Immunopathological Diseases and Therapeutics
SJR: 0.309 SNIP: 0.041 CiteScore™: 0.18

ISSN Print: 2151-8017
ISSN Online: 2151-8025

Archives: Volume 1, 2010 to Volume 7, 2016

Forum on Immunopathological Diseases and Therapeutics

DOI: 10.1615/ForumImmunDisTher.2014011238
pages 197-212

Structure and Biological Activity of Botulinum Neurotoxins and Application to Cancer Therapy

Kei Roger Aoki
Neurotoxin Research Program, Discovery Research Biological Sciences, Allergan, Inc., Irvine, California
Ester Fernandez-Salas
Department of Pathology, School of Medicine, University of Michigan, Ann Arbor, Michigan

ABSTRACT

Botulinum neurotoxin (BoNT) has historically been studied as the botulism-causing protein produced by the anaerobic bacillus, Clostridium botulinum. However, research interest in BoNT has recently shifted toward the mechanisms by which it can be utilized to decipher basic neuronal biology, treat neuromuscular disorders and pain, and be used as an anticancer treatment. BoNT has been shown to inhibit the release of neurotransmitters and factors required for tumor growth and maintenance, altering the tumor microenvironment. Treatment with BoNT can also enhance the delivery of chemotherapeutic agents, serve as an adjuvant to cancer chemotherapy, mitigate cancer-related side effects (i.e., pain and excess saliva), and potentiate the effects of radiotherapy. Most recently, work with BoNT has focused on the direct effects of the toxin in tumor cells. Through protein retargeting and recombinant technology, the activity of BoNT can be specifically delivered to cancer cells. This review summarizes the variety of ways in which BoNT has been used as an adjuvant for cancer therapy, discusses the potential mechanisms that describe how BoNT may affect growth and apoptosis of tumor cells, and highlights the promise these new biomolecules have as a safer and more effective anticancer therapeutic.


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