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Rapamycin targets the m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1 complex alone. Despite initial excitement, rapamycin and its analogues, everolimus and temsirolimus, have displayed limited efficacy in the treatment of lymphoid malignancies. This review highlights the important and well\u2010described aspects of the critical phosphatidylinositol\u20104,5\u2010bisphosphate 3\u2010kinase (PI3K)\/AKT\/m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content>pathway and discusses the mechanisms of action of rapamycin, its clinical efficacy in lymphoid malignancies, and the mechanisms of resistance. Renewed interest in targeting the pathway has evolved through the discovery of m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>2, a protein complex associated with a key mechanism of resistance to first generation mTOR inhibitors. As such, novel dual inhibitors of m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1 and<jats:styled-content style=\"fixed-case\">mTORC<\/jats:styled-content>2 have been developed, along with other dual inhibitors of the m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content>pathway. The evolution in the development of dual inhibitors is described herein, along with the burgeoning<jats:italic>in vitro<\/jats:italic>, pre\u2010clinical data and the early phase clinical data available. Although historically m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content>inhibitors have been used extensively in haematopoietic and solid organ transplant prophylaxis, this review will focus on developments of their use in lymphoid malignancies.<\/jats:p>","DOI":"10.1111\/bjh.12945","type":"journal-article","created":{"date-parts":[[2014,5,19]],"date-time":"2014-05-19T13:46:32Z","timestamp":1400507192000},"page":"336-351","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Time now to<scp>TORC<\/scp>the<scp>TORC<\/scp>? 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