The relevance of the advances
made around Warburg effect as a cause or consequence of tumorigenesis are promising
in the fight against cancer (Razungles
et al., 2013). Studies have shown that oxidative phosphorylation was not
fully suppressed during carcinogenesis, it could be partly turned on under
nutrient deficiency (Smolková
et al., 2011). It is now apparent that targeting both aerobic
glycolysis and mitochondrial metabolism may be required (Flaveny et al., 2015).
As described earlier LDH is the key enzyme in aerobic glycolysis and it
has long been noted that LDHA expression is upregulated in human neoplastic
cells. In fact, serum LDH concentrations correlate with tumor progression and
poor outcome. A research has proved that the overall survival of patients with
advanced pancreatic cancer, a disease with the median survival time of 6 months,
being the most lethal cancer, concluded that high LDH was associated with
systemic inflammation in these patients and had a prognostic value (Goldman et al., 1964).
Cancer cells are mechanically very resistant, and LDH is not cancer specific.
Also, the elevated LDH could be a result of damage to cells adjacent to the
cancerous cells, these theories are for further investigations, but LDHA is in
no doubt important for cancer survival.
Sodium oxamate is a structural analog of pyruvate (active substance:
oxamate) and competitive inhibitor of LDHA thereby one might expect that it can
disrupt gluconeogenesis and glycolysis, interrupting the established metabolic
pathways of the tumor cells and inhibit the protective autophagy in transformed
cells (Zhao et al., 2013)