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      Is Open Access

      Current Biochemical Applications and Future Prospects of Chlorotoxin in Cancer Diagnostics and Therapeutics

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          Abstract

          Chlorotoxin (CTX) is a minute 4 kDa protein made up of 36 amino acid residues, commonly known for its binding affinity to chloride channels and matrix metalloproteinase-2 (MMP-2) of glioma tumors of the spine and brain. This property and the possibility of conjugating this peptide to nanoparticles have enabled its diverse use in various biotechnological and biomedical applications for cancer treatment, such as in tumor imaging and radiotherapy. Because of the fascinating biological properties CTX possesses, elucidating its mechanism of action may hold promise for the development of new and effective therapeutic drugs, as well as more sensitive and highly specific cancer-screening kits. This article therefore reviews the currently known applications of CTX and suggests diverse ways in which it can be applied for the design of improved drugs and diagnostic tools for cancer.

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          Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting.

          Chrisostomi Gialeli, Achilleas Theocharis, Nikos K Karamanos (2011)
          Matrix metalloproteinases (MMPs) consist of a multigene family of zinc-dependent extracellular matrix (ECM) remodeling endopeptidases implicated in pathological processes, such as carcinogenesis. In this regard, their activity plays a pivotal role in tumor growth and the multistep processes of invasion and metastasis, including proteolytic degradation of ECM, alteration of the cell-cell and cell-ECM interactions, migration and angiogenesis. The underlying premise of the current minireview is that MMPs are able to proteolytically process substrates in the extracellular milieu and, in so doing, promote tumor progression. However, certain members of the MMP family exert contradicting roles at different stages during cancer progression, depending among other factors on the tumor stage, tumor site, enzyme localization and substrate profile. MMPs are therefore amenable to therapeutic intervention by synthetic and natural inhibitors, providing perspectives for future studies. Multiple therapeutic agents, called matrix metalloproteinase inhibitors (MMPIs) have been developed to target MMPs, attempting to control their enzymatic activity. Even though clinical trials with these compounds do not show the expected results in most cases, the field of MMPIs is ongoing. This minireview critically evaluates the role of MMPs in relation to cancer progression, and highlights the challenges, as well as future prospects, for the design, development and efficacy of MMPIs. © 2010 The Authors Journal compilation © 2010 FEBS.
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            Natural products in drug discovery.

            Alan Harvey (2008)
            Natural products have been the single most productive source of leads for the development of drugs. Over a 100 new products are in clinical development, particularly as anti-cancer agents and anti-infectives. Application of molecular biological techniques is increasing the availability of novel compounds that can be conveniently produced in bacteria or yeasts, and combinatorial chemistry approaches are being based on natural product scaffolds to create screening libraries that closely resemble drug-like compounds. Various screening approaches are being developed to improve the ease with which natural products can be used in drug discovery campaigns, and data mining and virtual screening techniques are also being applied to databases of natural products. It is hoped that the more efficient and effective application of natural products will improve the drug discovery process.
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              Breast cancer as a systemic disease: a view of metastasis.

              A J Redig, S McAllister (2013)
              Breast cancer is now the most frequently diagnosed cancer and leading cause of cancer death in women worldwide. Strategies targeting the primary tumour have markedly improved, but systemic treatments to prevent metastasis are less effective; metastatic disease remains the underlying cause of death in the majority of patients with breast cancer who succumb to their disease. The long latency period between initial treatment and eventual recurrence in some patients suggests that a tumour may both alter and respond to the host systemic environment to facilitate and sustain disease progression. Results from studies in animal models suggest that specific subtypes of breast cancer may direct metastasis through recruitment and activation of haematopoietic cells. In this review, we focus on data implicating breast cancer as a systemic disease. © 2013 The Association for the Publication of the Journal of Internal Medicine.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Adv Pharm Bull
                Journal ID (iso-abbrev): Adv Pharm Bull
                Journal ID (publisher-id): Adv Pharm Bull
                Journal ID (pmc): APB
                Journal ID (publisher-id): TBZMED
                Title: Advanced Pharmaceutical Bulletin
                Publisher: Tabriz University of Medical Sciences
                ISSN (Print): 2228-5881
                ISSN (Electronic): 2251-7308
                Publication date (Print): October 2019
                Publication date (Electronic): 24 October 2019
                Volume: 9
                Issue: 4
                Pages: 510-520
                Affiliations
                1Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, Faculty of Science and Agriculture, University of Zululand, KwaDlangezwa 3886, South Africa.
                2Department of Biochemistry, College of Sciences, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria.
                Author notes
                [* ] Corresponding Author: Abidemi Paul Kappo, Tel (Office): +27-35-902-6780, Fax: +27-35-902-6568, Email: KappoA@ 123456unizulu.ac.za
                Author information
                https://orcid.org/0000-0003-2333-2940
                https://orcid.org/0000-0003-1329-1057
                https://orcid.org/0000-0003-2165-7936
                https://orcid.org/0000-0003-2521-8957
                Article
                DOI: 10.15171/apb.2019.061
                PMC ID: 6912174
                PubMed ID: 31857956
                SO-VID: 525cc2a3-c327-42d8-bc4a-a0aa21da829c
                Copyright © © 2019 The Author (s)
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, as long as the original authors and source are cited. No permission is required from the authors or the publishers.

                History
                Date received : 29 April 2019
                Date revision received : 14 July 2019
                Date accepted : 21 July 2019
                Page count
                Figures: 1, Tables: 1, References: 106, Pages: 11
                Categories
                Subject: Review Article

                Keywords: cancer,chlorotoxin,diagnostics,matrix metalloproteinase-2,therapeutics,tumor
                Data availability:
                Keywords: cancer, chlorotoxin, diagnostics, matrix metalloproteinase-2, therapeutics, tumor

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