Hyponatremia, the phenomenon of serum
sodium level falling below 135 mmol/L, is seen frequently in
cancer patients and has been correlated with poor prognosis.
Hyponatremia has classically been attributed to the "syndrome of inappropriate
antidiuretic hormone secretion," leading to prolonged fluid retention. However, this is unlikely to be the only mechanism. In this study, we advance the hypothesis that upregulation of various
sodium-transporting
proteins during the
cancer process makes a significant contribution to the pathophysiology of
cancer-associated
hyponatremia. Such
sodium-transporting
proteins include
voltage-gated sodium channels, especially its
hypoxia-promoted persistent current,
epithelial sodium channels, and
transient receptor potential channels. Thus,
hyponatremia follows
cancer, whereby drop in blood serum level occurs as a result of uptake of
sodium from extracellular fluid by
cancer cells. Indeed, the
sodium content of
cancer cells/tissues is higher than normal. In turn, the rise in the intracellular
sodium concentration brings about a range of cellular effects, including extracellular acidification that promotes invasiveness and thus leads to poor prognosis. This perspective offers novel
therapies for
cancer and the associated
hyponatremia.