Despite the fact that the majority of lymphomas initially respond to treatment, many patients relapse and die from disease that is refractory to current regimens. The need for new treatment strategies in lymphomas has led to the investigation and evaluation of novel agents that target cellular pathways. The mammalian target of rapamycin (mTOR) is a representative pathway that may be implicated in lymphomagenesis. Rapamycin and especially its derivatives (temsirolimus, everolimus, and deforolimus) represent the first described mTOR inhibitors. These agents have shown promising results in the treatment of lymphoid malignancies. On the other hand, new ATP-competitive mTOR inhibitors that provoke a broader inhibition of mTOR activity are in early stages of clinical development. The purpose of this paper is to summarize the existing knowledge about mTOR inhibitors and their use in the treatment of B-cell lymphomas. Relevant issues regarding mTOR biology in general as well as in B-cell lymphoid neoplasms are also discussed in short. 1. Introduction Current approaches in treating lymphoid malignancies have focused on the development of therapeutic regimens that selectively target dysregulated signal transduction pathways in neoplastic cells. Among aberrantly activated signaling cascades that are implicated in the pathogenesis of lymphomas is the mammalian target of rapamycin (mTOR) pathway, which is involved in many vital cellular processes [1]. Rapamycin and its analogs (rapalogs) comprise the classical mTOR inhibitors. A number of completed as well as other ongoing preclinical and clinical trials have tested these drugs in lymphomas, either as monotherapy or in combination with established chemotherapy [1]. Moreover, other anti-mTOR molecules, such as specific active-site TOR inhibitors (asTORi), with better pharmacological profiles are candidate drugs to be tested in clinical trials against lymphoid malignancies [2]. Herein we aim to review the results of trials with mTOR inhibitors in B-cell lymphomas. Firstly, the mTOR signaling network as well as possible aetiologic factors of aberrant activation of the mTORC1 signaling cascade in B-cell lymphoid malignancies are discussed in short. 2. mTOR Signaling Network Rapamycin (also known as sirolimus or Rapamune, Wyeth) is the first described mTOR inhibitor [3]. This drug, originally developed as an antifungal agent, was soon found to have immunosuppressive and antineoplasmatic actions [4]. Systemic efforts to decipher the molecular mechanisms of these actions led to the isolation of the mTOR protein and the
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