mTOR inhibitors: A novel class of anti-cancer agents

Excerpt

Mammalian Target of Rapamycin (mTOR) is a serine/threonine protein kinase that acts as a master switch between anabolic and catabolic functions of the human body in pathways stimulated by insulin, growth factors and mitogen [1]. mTOR functions as a central controller of growth, proliferation, metabolism and angiogenesis, but its signaling is dysregulated in various human diseases especially certain cancers like renal cell carcinoma and breast cancer [2]. In cancer, mTOR is frequently hyperactivated which promotes cancer development and progression. In certain cancers, resistance to antineoplastic agents such as topoisomerase 1, topoisomerase 2 inhibitors and methotrexate can be overcome with a synergistic combination with mTOR inhibitors [3, 4]. Furthermore, mTOR activates the degradation of cyclin dependent kinases such as CDK1 which increases synthesis of dihydrofolate reductases. By decreasing this enzyme, mTOR inhibitors like sirolimus and temsirolimus, promote tumour sensitivity to agents such as methotrexate [4]. …