Chemical Metabolic Inhibitors for the Treatment of Blood-Borne Cancers
Martin Villalba, Nuria Lopez-Royuela, Ewelina Krzywinska, Moeez G. Rathore, Robert A. Hipskind, Houda Haouas and Nerea Allende-Vega
Affiliation: Martin Villalba, INSERM U1040, Institut de Recherche en Biothérapie, 80, avenue Augustin Fliche. 34295 Montpellier Cedex 5, France.
Keywords: Cancer immunosurveillance, DCA, glutamine, metformin, MHC-I, OXPHOS, warburg effect.
Tumor cells, including leukemic cells, remodel their bioenergetic system in favor of aerobic glycolysis. This process is called
“the Warburg effect” and offers an attractive pharmacological target to preferentially eliminate malignant cells. In addition, recent results
show that metabolic changes can be linked to tumor immune evasion. Mouse models demonstrate the importance of this metabolic
remodeling in leukemogenesis. Some leukemias, although treatable, remain incurable and resistance to chemotherapy produces an
elevated percentage of relapse in most leukemia cases. Several groups have targeted the specific metabolism of leukemia cells in
preclinical and clinical studies to improve the prognosis of these patients, i.e. using L-asparaginase to treat pediatric acute lymphocytic
leukemia (ALL). Additional metabolic drugs that are currently being used to treat other diseases or tumors could also be exploited for
leukemia, based on preclinical studies. Finally, we discuss the potential use of several metabolic drugs in combination therapies,
including immunomodulatory drugs (IMiDs) or immune cell-based therapies, to increase their efficacy and reduce side effects in the
treatment of hematological cancers.
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