Chemical metabolic inhibitors for the treatment of blood-borne cancers.
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.
Martin
M
Villalba
Nuria
N
Lopez-Royuela
Ewelina
E
Krzywinska
Moeez G
MG
Rathore
Robert A
RA
Hipskind
Houda
H
Haouas
INSERM U1040, Institut de Recherche en Biothérapie, 80, avenue Augustin Fliche. 34295 Montpellier Cedex 5, France. martin.villalba@inserm.fr.
Nerea
N
Allende-Vega
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017690:Cell Transplantation / Q000379:methods; D003131:Combined Modality Therapy; D005973:Glutamine / Q000378:metabolism; D006019:Glycolysis; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation; D007938:Leukemia / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D010085:Oxidative Phosphorylation; D037761:Sirtuins / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation
D000970:Antineoplastic Agents; D015395:Histocompatibility Antigens Class I; D005973:Glutamine; D037761:Sirtuins; D006655:Histone Deacetylases