Advanced stage tumors were once thought to contain uniform cell types throughout. This theory was recently discovered to be a myth and in fact these advanced tumors contain oxygen rich (aerobic) and oxygen deficient (hypoxic) regions. Once this advanced stage tumor develops the hypoxic region it is generally resistant to standard chemotherapy and radiation protocols, resulting in treatment failure, relapse and patient mortality. Hypoxic and aerobic regions of the tumor each have unique metabolic processes that are essential to their survival. Under hypoxic conditions, cancer cells metabolize glucose into lactate, whereas nearby aerobic cells take up this lactate for oxidative phosphorylation for ATP production. The transport of these metabolites occurs through a membrane transporter called the mono-carboxylate transporter 1 (MCT1). Inhibition of this MCT1 transporter has remarkable clinical potential. Recently, we have designed, synthesized and evaluated several small molecules as MCT1 inhibitors. Our synthetic and biological studies will be presented.

Design, synthesis, and evaluation of novel small molecules as mono carboxylate transporter 1 inhibitors

244th National Meeting (2012)

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