Carbonic Anhydrase Isozymes as Diagnostic Biomarkers and Therapeutic Targets

Abstract

The early immunohistochemical studies of carbonic anhydrases (CAs) were mainly focused on their normal tissue distribution. Only a few studies included samples from pathologic diseases, particularly cancer. This line of research remained inactive until the discovery of CA IX—the first cancer-associated isozyme. The association of CA IX with hypoxic regions of tumors became obvious, and experimental results confirmed hypoxia regulation. CA IX is now widely considered a biomarker of tumor hypoxia and prognosis. Even though it has several characteristics of a promising biomarker, the implementation of CA IX in clinical pathology has progressed slowly. CA IX research has also produced promising therapeutic molecules, some of which are already in clinical trials. CA XII is another cancer-associated isozyme; however, it is not yet used as a clinical biomarker in routine diagnostics nor is it utilized in therapeutic applications. Surprisingly, the well-known isozyme CA II has turned out to be an attractive candidate as a diagnostic marker, at least in the special case of gastrointestinal stromal tumors. As a conclusion, certain CA isozymes have definite promise as histopathological markers and therapeutic targets. Even though the implementation of new approaches is a slow process in clinical medicine, the first step has been taken to utilize the unique properties of CA isozymes in diagnostics and therapy.