Dysregulated proton and sodium gradients highlight cancer invasion and proliferation

Acidity and salinity of the extracellular fluid, reflecting degrees of acid and sodium contents respectively, regulate essential cellular functions in health and disease, especially cancer. Tumor invasiveness is enhanced by the acidic extracellular milieu as a consequence of upregulated aerobic glycolysis. But recent discoveries also suggest that enhanced proliferative mitosis, which also hallmarks cancer, is impacted by interstitial salinity. Abnormal transmembrane proton/sodium gradients lead to pathophysiological alterations at the cellular level. These novel perspectives mandate pioneering imaging of extracellular acidity and salinity, preferably monitored simultaneously. By dissecting the interplay between dysregulated pH and electrolyte imbalance within the tumor habitat, these biomarkers hold promise for early cancer diagnosis and tracking therapies, from chemotherapy to immunotherapy.