Carbonic anhydrase inhibition as a cancer therapy: a review of patent literature 2007-2009

Abstract

Importance of the field: The functional contribution of membrane-bound extracellular carbonic anhydrases (CAs) to hypoxic tumor growth and progression has long been hypothesized; however, recent convergent evidence from a number of groups strongly implicates these CAs as key prosurvival enzymes during tumor hypoxia. From this perspective targeting the inhibition of cancer-associated CA enzymes, most notably CA IX and XII, has recently been identified as a mechanistically novel scientific opportunity with great potential as a new cancer drug target. Areas covered in this review: This review covers world patent applications filed during the 2007 - 2009 period for small molecule approaches; non-small molecule approaches are not within the scope of this review. What the reader will gain: The reader will be provided with a background of the biology of CAs as well as the recent research findings that have validated the crucial prosurvival role of CAs in hypoxic tumors. The review will highlight small molecule molecular methods that modulate CAs as an anti-cancer therapeutic strategy. Take home message: Much of what has been reported in the patent literature during the period 2007 - 2009 is based on alleged therapeutic benefits of CA inhibitors in cancer. Recently appropriate CA-relevant cell and animal models of tumor hypoxia for the evaluation of compounds have become available and the verification of the ability of small molecules to modulate CA activity as a cancer therapy or as a diagnostic and/or prognostic tool is now possible and probable. The CA field will thus provide for a scientifically exciting and possibly rewarding next few years, accelerated by the growing interest in the potential clinical applications of this enzyme class in oncology.