title: Reviving Lonidamine and 6-Diazo-5-oxo-L-norleucine to Be Used in Combination for Metabolic Cancer Therapy.
abstract: Abnormal metabolism is another cancer hallmark. The two most characterized altered metabolic pathways are high rates of glycolysis and glutaminolysis, which are natural targets for cancer therapy. Currently, a number of newer compounds to block glycolysis and glutaminolysis are being developed; nevertheless, lonidamine and 6-diazo-5-oxo-L-norleucine (DON) are two old drugs well characterized as inhibitors of glycolysis and glutaminolysis, respectively, whose clinical development was abandoned years ago when the importance of cancer metabolism was not fully appreciated and clinical trial methodology was less developed. In this review, a PubMed search using the words lonidamine and 6-diazo-5-oxo-L-norleucine (DON) was undertaken to analyse existing information on the preclinical and clinical studies of these drugs for cancer treatment. Data show that they exhibit antitumor effects; besides there is also the suggestion that they are synergistic. We conclude that lonidamine and DON are safe and potentially effective drugs that need to be reevaluated in combination as metabolic therapy of cancer.
authors.affiliation: Instituto Nacional de Cancerología, 14080 Mexico City, DF, Mexico.
authors.forename: Diana
authors.initials: D
authors.lastname: Cervantes-Madrid
authors.affiliation: Facultad de Ciencias, Universidad Nacional Autónoma de México, 04510 Mexico City, DF, Mexico.
authors.forename: Yair
authors.initials: Y
authors.lastname: Romero
authors.affiliation: Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/Instituto Nacional de Cancerología, 14080 Mexico City, DF, Mexico.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Dueñas-González
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003980:Diazooxonorleucine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007191:Indazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D007191:Indazoles; D003980:Diazooxonorleucine; C016371:lonidamine