Rapamycin and tumor growth: mechanisms behind its anticancer activity

In the past few years, a heightened awareness has developed toward the problem of cancer occurrence and treatment in organ transplant recipients under immunosuppression. Treatment and prevention of cancer in transplant patients with an intentionally suppressed immune system are generally not considered an ideal situation because intact immunity is important for recognizing and destroying potentially neoplastic cells. Nonetheless, recent studies indicate that fighting tumors is not impossible under conditions of immune suppression, and in fact, immunosuppressive agents have been discovered that possess potent anticancer effects. In particular, one class of immunosuppressants, referred to as mammalian target of rapamycin (mTOR) inhibitors (mTORi), has experimentally shown an ability to suppress the immune system to protect allografts from rejection while simultaneously inhibiting tumor growth. To gain a better understanding of this dual effect, we will review the key intracellular signaling pathways controlled by mTOR. We will discuss how mTORi affects the growth and survival of a variety of nonimmune cells, with a special emphasis on cancer. A better understanding of mTOR-related pathways and the repertoire of normal and neoplastic cells affected by mTORi will likely improve our ability to treat transplant rejection, cancer, and other pathological conditions.