Lonidamine, a derivate of
indazole-3-carboxylic acid, is an
antineoplastic drug with a typical mechanism of action.
Lonidamine has no function on cellular
nucleic acids or
protein synthesis, whereas it exerts a powerful inhibitory effect on oxygen consumption, aerobic glycolysis and
lactate transport and accumulation of neoplastic cells. Nevertheless, its proven ability to modify the permeability of membranes is consistent with the possible increase of
drug uptake, reverse of drug resistance and triggering of apoptotic pathway.
Lonidamine has been experimentally shown to potentiate the cytotoxic effects of
anthracyclines in human
breast cancer cell lines and
cisplatin activity in both
platinum-sensitive and
platinum-resistant human ovarian
carcinoma cell lines. Since the specific mechanism of action and side effects are not overlapping with those of standard
antineoplastic agents, combination of
lonidamine with standard
chemotherapy has been widely investigated for the treatment of solid
tumors. Additionally, the enhancement of
radiotherapy activity by
lonidamine has been considered for
palliative therapy of lesions from metastatic
cancers. The encouraging results of phase II-III trials for the treatment of advanced breast, ovarian and
lung cancer must be confirmed by larger studies. Specifically designed studies to address the role of
lonidamine in the adjuvant setting are warranted.
Lonidamine, a dechlorinate derivative of
indazole-3-carboxylic acid, has proved to exert a powerful antiproliferative effect and to impair the energy metabolism of neoplastic cells. Herein we review the current experience on combining
lonidamine and
chemotherapy and/or
radiation therapy in the treatment of solid
tumors. Several studies have been published on this topic. The total number of trials reported in literature and length of follow-up are still insufficient to draw a firm conclusion. However, the available data demonstrate a significant role of
lonidamine in modulating
anthracycline and
platinum compound activity.