The article discusses the therapeutic potential of targeting pH regulation in tumours, a strategy that has not been widely explored by traditional cancer drugs. Tumour cells, due to their high metabolic rate and hypoxic environment, have evolved mechanisms to function in acidic conditions. Key pH regulators in tumour cells include various isoforms of carbonic anhydrase (CA), anion exchangers, Na+/HCO3− co-transporters, Na+/H+ exchangers, monocarboxylate transporters, and the vacuolar ATPase (V-ATPase). These proteins are involved in maintaining intracellular pH (pH_i) and extracellular pH (pH_e), which is crucial for tumour growth and metastasis. The Warburg effect, where cancer cells prefer glycolysis over oxidative phosphorylation, leads to increased lactic acid production and tumour acidification. This acidic environment is further exacerbated by the overexpression of CA9 and CA12, which are associated with cancer progression and response to therapy. Tumour cells have developed mechanisms to counteract this acidity, such as exporting protons and maintaining an alkaline intracellular pH. However, this pH regulation also contributes to the tumour microenvironment, promoting angiogenesis and metastasis. Several therapeutic strategies are being explored to target these pH regulators. Carbonic anhydrase inhibitors, such as sulphonamides and coumarins, are effective in inhibiting CA9 and CA12, leading to reduced tumour acidification and growth. Monoclonal antibodies targeting CA9 and CA12 are also under development, showing promise in preclinical studies. Additionally, V-ATPase inhibitors and proton pump inhibitors (PPIs) are being investigated for their potential to disrupt tumour pH regulation. Other pH-regulating proteins, such as anion exchangers, Na+/H+ exchangers, and monocarboxylate transporters (MCTs), are also being targeted. Inhibitors of these proteins can disrupt tumour acidification and inhibit cancer cell growth. The article highlights the importance of understanding the complex interplay of these proteins in tumour biology and the potential of targeting them as a novel therapeutic approach. Current research is focused on developing selective inhibitors and monoclonal antibodies that can effectively target these proteins without causing significant toxicity in normal tissues. The potential of these strategies in cancer treatment is promising, with several compounds in various stages of clinical development.The article discusses the therapeutic potential of targeting pH regulation in tumours, a strategy that has not been widely explored by traditional cancer drugs. Tumour cells, due to their high metabolic rate and hypoxic environment, have evolved mechanisms to function in acidic conditions. Key pH regulators in tumour cells include various isoforms of carbonic anhydrase (CA), anion exchangers, Na+/HCO3− co-transporters, Na+/H+ exchangers, monocarboxylate transporters, and the vacuolar ATPase (V-ATPase). These proteins are involved in maintaining intracellular pH (pH_i) and extracellular pH (pH_e), which is crucial for tumour growth and metastasis. The Warburg effect, where cancer cells prefer glycolysis over oxidative phosphorylation, leads to increased lactic acid production and tumour acidification. This acidic environment is further exacerbated by the overexpression of CA9 and CA12, which are associated with cancer progression and response to therapy. Tumour cells have developed mechanisms to counteract this acidity, such as exporting protons and maintaining an alkaline intracellular pH. However, this pH regulation also contributes to the tumour microenvironment, promoting angiogenesis and metastasis. Several therapeutic strategies are being explored to target these pH regulators. Carbonic anhydrase inhibitors, such as sulphonamides and coumarins, are effective in inhibiting CA9 and CA12, leading to reduced tumour acidification and growth. Monoclonal antibodies targeting CA9 and CA12 are also under development, showing promise in preclinical studies. Additionally, V-ATPase inhibitors and proton pump inhibitors (PPIs) are being investigated for their potential to disrupt tumour pH regulation. Other pH-regulating proteins, such as anion exchangers, Na+/H+ exchangers, and monocarboxylate transporters (MCTs), are also being targeted. Inhibitors of these proteins can disrupt tumour acidification and inhibit cancer cell growth. The article highlights the importance of understanding the complex interplay of these proteins in tumour biology and the potential of targeting them as a novel therapeutic approach. Current research is focused on developing selective inhibitors and monoclonal antibodies that can effectively target these proteins without causing significant toxicity in normal tissues. The potential of these strategies in cancer treatment is promising, with several compounds in various stages of clinical development.