Dichloroacetate (DCA) in Osteosarcoma: A non-toxic agent targeting cancer metabolism.

Osteosarcoma (OS) is the most common primary solid tumor of bone in children and young adults and with only a 60-70% 5-year survival rate (taH09). Approximately 20% of OS patients present with metastatic disease, and 80% of deaths are caused by lung metastases, thus there is a real need to focus on understanding and treating the metastatic process to improve outcomes (taH09, broadheadM11).Deregulated metabolism has recently been recognised as a new hallmark of cancer, and is now widely accepted as an important target for cancer therapy (hanahan11, Galluzzi13). The cancer metabolic phenotype includes the glycolytic phenotype or Warburg effect, where cells increase glycolysis while decreasing mitochondrial activity (Fig1A) (vanderheidenM09). In addition to promoting tumour growth and survival, altered metabolism is increasingly being linked to adverse cell characteristics, such as metastasis, drug resistance and stem-like behaviours (LuJ15,riesterM17