Repositioning Mefloquine as an Anticancer Drug: An Evidence-Based Review

Abstract: Drug repurposing has gained significant attention in recent years, particularly in cancer research, due to its potential to develop innovative therapeutics. This approach offers cost-effective strategies while bypassing some of the stringent regulatory hurdles imposed by the Food and Drug Administration (FDA). Mefloquine has been extensively investigated since 1960 and was approved by the FDA in 1989 for the treatment of malaria. Recently, Mefloquine has been rediscovered for its anticancer effects. Collective data from a plethora of research reports show that Mefloquine exhibits anticancer activity in preclinical models against a wide range of human malignancies, including gastric and colorectal cancer, prostate cancer, cervical cancer, breast cancer, glioblastoma and neuroblastoma, acute and chronic myeloid leukemia, esophageal and oral squamous carcinoma through different molecular mechanisms in both in vitro and in vivo study models. In addition to apoptosis, it has been shown to set the cancer cells on the road to ruin via induction of autophagy and ferroptosis, making it a promising drug for killing apoptosis-resistant cancer cells. Apart from its anticancer effects as a single agent, mefloquine has been shown to improve the efficacy of clinical cancer drugs in various study models when used in combination therapy. Keeping in view the aforesaid research findings, Mefloquine may warrant further investigation for potential repurposing in cancer therapy, either as monotherapy or in combination with other clinically practiced chemotherapeutics.