An update on anticancer drug development and delivery targeting carbonic anhydrase IX

The expression of carbonic anhydrase (CA) IX is up-regulated in many types of solid tumors in humans under hypoxic and acidic microenvironment. Inhibition of CA IX enzymatic activity with selective inhibitors, antibodies or labeled probes has been shown to reverse the acidic environment of solid tum...

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Bibliographic Details
Published in:PeerJ (San Francisco, CA) CA), 2017-11, Vol.5, p.e4068-e4068, Article e4068
Main Authors: Kazokaitė, Justina, Aspatwar, Ashok, Parkkila, Seppo, Matulis, Daumantas
Format: Article
Language:English
Subjects:
Acidification
Analysis
Angiogenesis
Animal models
Antineoplastic agents
Antitumor agents
Biochemistry
Biophysics
CA IX antitumor agents
CA IX monoclonal antibodies
Cancer therapies
Carbonic anhydrase
Carbonic anhydrase IX
Carbonic anhydrases
Carcinogenesis
Cell growth
Chemotherapy
Conjugated probes
Drug delivery
Drug development
Drugs and Devices
Enzymatic activity
Enzymes
Hydration
Hypoxia
Hypoxic tumors
Medical research
Metastasis
Monoclonal antibodies
Oocytes
Pharmacological research
Product development
Properties
Proteins
Solid tumors
Stem cells
Tumorigenesis
Tumors
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Summary:The expression of carbonic anhydrase (CA) IX is up-regulated in many types of solid tumors in humans under hypoxic and acidic microenvironment. Inhibition of CA IX enzymatic activity with selective inhibitors, antibodies or labeled probes has been shown to reverse the acidic environment of solid tumors and reduce the tumor growth establishing the significant role of CA IX in tumorigenesis. Thus, the development of potent antitumor drugs targeting CA IX with minimal toxic effects is important for the target-specific tumor therapy. Recently, several promising antitumor agents against CA IX have been developed to treat certain types of cancers in combination with radiation and chemotherapy. Here we review the inhibition of CA IX by small molecule compounds and monoclonal antibodies. The methods of enzymatic assays, biophysical methods, animal models including zebrafish and oocytes, and techniques of diagnostic imaging to detect hypoxic tumors using CA IX-targeted conjugates are discussed with the aim to overview the recent progress related to novel therapeutic agents that target CA IX in hypoxic tumors.
ISSN:2167-8359
2167-8359
DOI:10.7717/peerj.4068