29 March 2024 | Alaa Tafech and Angélique Stéphanou
This review explores the significance of acidity in cancer cells and its impact on cancer therapy. Cancer cells exhibit high glycolytic activity, leading to acidification of the tumor microenvironment. This acidity enhances tumor aggressiveness, invasiveness, and metastasis, contributing to poor clinical outcomes. The review discusses the mechanisms by which cancer cells adapt to acidic conditions, including the activation of transporters like CAIX, NHE1, MCT4, and V-ATPase to maintain intracellular pH. It highlights the challenges in measuring intracellular pH and the role of acidity in tumor development, such as promoting tumor invasion, cellular plasticity, and immunosuppression. The review also examines the Warburg effect, where cancer cells prefer aerobic glycolysis over oxidative phosphorylation, and how acidity can influence this process. Finally, it discusses the potential of targeting acidity in cancer therapy, including strategies to improve drug uptake and enhance therapeutic efficacy.This review explores the significance of acidity in cancer cells and its impact on cancer therapy. Cancer cells exhibit high glycolytic activity, leading to acidification of the tumor microenvironment. This acidity enhances tumor aggressiveness, invasiveness, and metastasis, contributing to poor clinical outcomes. The review discusses the mechanisms by which cancer cells adapt to acidic conditions, including the activation of transporters like CAIX, NHE1, MCT4, and V-ATPase to maintain intracellular pH. It highlights the challenges in measuring intracellular pH and the role of acidity in tumor development, such as promoting tumor invasion, cellular plasticity, and immunosuppression. The review also examines the Warburg effect, where cancer cells prefer aerobic glycolysis over oxidative phosphorylation, and how acidity can influence this process. Finally, it discusses the potential of targeting acidity in cancer therapy, including strategies to improve drug uptake and enhance therapeutic efficacy.