Hyponatremia and Cancer: From Bedside to Benchside

SIMPLE SUMMARY: This review article is focused on hyponatremia in cancer patients. Hyponatremia is the most common electrolyte disorder in these patients and there is evidence that it negatively affects the course of the disease. Basic research has shown an increased proliferation rate and motility of cells cultured in low [Na(+)] conditions. Interestingly, the vasopressin receptor antagonist tolvaptan, originally approved for the treatment of hyponatremia secondary to the syndrome of inappropriate antidiuresis, and subsequently in polycystic kidney disease, counteracts cancer cell proliferation and invasivity in vitro. This result might encourage the design of clinical trials to determine whether tolvaptan may also have a role against cancer on clinical grounds. ABSTRACT: Hyponatremia is the most common electrolyte disorder encountered in hospitalized patients. This applies also to cancer patients. Multiple causes can lead to hyponatremia, but most frequently this electrolyte disorder is due to the syndrome of inappropriate antidiuresis. In cancer patients, this syndrome is mostly secondary to ectopic secretion of arginine vasopressin by tumoral cells. In addition, several chemotherapeutic drugs induce the release of arginine vasopressin by the hypothalamus. There is evidence that hyponatremia is associated to a more negative outcome in several pathologies, including cancer. Many studies have demonstrated that in different cancer types, both progression-free survival and overall survival are negatively affected by hyponatremia, whereas the correction of serum [Na(+)] has a positive effect on patient outcome. In vitro studies have shown that cells grown in low [Na(+)] have a greater proliferation rate and motility, due to a dysregulation in intracellular signalling pathways. Noteworthy, vasopressin receptors antagonists, which were approved more than a decade ago for the treatment of euvolemic and hypervolemic hyponatremia, have shown unexpected antiproliferative effects. Because of this property, vaptans were also approved for the treatment of polycystic kidney disease. In vitro evidence indicated that this family of drugs effectively counteracts proliferation and invasivity of cancer cells, thus possibly opening a new scenario among the pharmacological strategies to treat cancer.