The potential of carbonic anhydrase enzymes as a novel target for anti-cancer treatment

Carbonic anhydrase (CA) is a zinc-dependent metal enzyme that maintains the pH and carbon dioxide (CO₂) homeostasis in cells by catalyzing the reversible hydration and dehydration of CO₂ and bicarbonate (HCO₃^-). In mammals, there are 16 isozymes of CA existed, namely CAI to CAXIV, but only 15 isozymes are found in humans except CAXV. Human CAs have highly conserved catalytic domains, all of which are distributed in different tissues and play important physiological roles. Changes in their functions may disrupt the typical distribution of CAs throughout human body and therefore CAs can be used as diagnostic biomarkers for many diseases. Furthermore, the expression of CAs is correlated to the progression of numerous tumors, therapeutic sensitivity and patient prognosis. In this review, we discuss thoroughly the structure of CAs, their functional activities in human physiology, dysregulations and diseases related to CAs, and different types of CA inhibitors that can reverse their dysregulation.