Exploring mammalian target of rapamycin (mTOR) inhibition for treatment of mantle cell lymphoma and other hematologic malignancies

References

• Abraham RT, Gibbons JJ. The mammalian target of rapamycin signaling pathway: twists and turns in the road to cancer therapy. Clin Cancer Res 2007;13:3109–3114.
   PubMed Web of Science ®Google Scholar
• Sehgal SN, Baker H, Vezina C. Rapamycin (AY-22,989), a new antifungal antibiotic. II. Fermentation, isolation and characterization. J Antibiot (Tokyo) 1975;28:727–732.
   PubMed Web of Science ®Google Scholar
• Sehgal SN. Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin Biochem 1998;31:335–340.
   PubMed Web of Science ®Google Scholar
• Bjornsti MA, Houghton PJ. The TOR pathway: a target for cancer therapy. Nat Rev Cancer 2004;4:335–348.
   PubMed Web of Science ®Google Scholar
• Trepanier DJ, Gallant H, Legatt DF, Yatscoff RW. Rapamycin: distribution, pharmacokinetics and therapeutic range investigations: an update. Clin Biochem 1998;31:345–351.
   PubMed Web of Science ®Google Scholar
• Teachey DT, Obzut DA, Cooperman J, et al The mTOR inhibitor CCI-779 induces apoptosis and inhibits growth in preclinical models of primary adult human ALL. Blood 2006;107:1149–1155.
   PubMed Web of Science ®Google Scholar
• Podsypanina K, Lee RT, Politis C, et al An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten +/− mice. Proc Natl Acad Sci USA 2001;98:10320–10325.
   PubMed Web of Science ®Google Scholar
• Neshat MS, Mellinghoff IK, Tran C, et al Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc Natl Acad Sci USA 2001;98:10314–10319.
   PubMed Web of Science ®Google Scholar
• Yu K, Toral-Barza L, Discafani C, et al mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer. Endocr Relat Cancer 2001;8:249–258.
   PubMed Web of Science ®Google Scholar
• Rivera VM, Kreisberg JI, Mita MM. Pharmacodynamic study of skin biopsy specimens in patients (pts) with refractory or advanced malignancies following administration of AP23573, an mTOR inhibitor. J Clin Oncol 2005 ASCO Ann Proc 2005;23: (Abstract 3033).
   Google Scholar
• Metcalf CA, Bohacek R, Rozamus LW. Structure-based design of AP23573, a phosphorous-containing analog of rapamycin for anti-tumor therapy. Proc Am Assoc Cancer Res 2008;45:2476.
   Google Scholar
• Clackson T, Metcalf CA, Rivera VM. Broad anti-tumor activity of ap23573, an mTOR inhibitor in clinical development. Proc Am Soc Clin Oncol 2003;22: (Abstract 882).
   Google Scholar
• Campbell RA, Sanchez E, Steinberg J. The mTOR inhibitor RAD001 (everolimus) inhibits myeloma tumor growth in vivo and enhances the anti-MM effects of bortezomib and arsenic trioxide. Blood 2007;110: (Abstract 4801).
   Web of Science ®Google Scholar
• Yazbeck VY, Buglio D, Georgakis GV, et al Temsirolimus downregulates p21 without altering cyclin D1 expression and induces autophagy and synergizes with vorinostat in mantle cell lymphoma. Exp Hematol 2008;36:443–450.
   PubMed Web of Science ®Google Scholar
• Hudes G, Carducci M, Tomczak P, et al Temsirolimus, interferon α, or both for advanced renal-cell carcinoma. N Engl J Med 2007;356:2271–2281.
   PubMed Web of Science ®Google Scholar
• Motzer RJ, Escudier B, Oudard S, et al Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372:449–456.
   PubMed Web of Science ®Google Scholar
• Mita MM, Mita AC, Chu QS, et al Phase I trial of the novel mammalian target of rapamycin inhibitor deforolimus (AP23573; MK-8669) administered intravenously daily for 5 days every 2 weeks to patients with advanced malignancies. J Clin Oncol 2008;26:361–367.
   PubMed Web of Science ®Google Scholar
• Hartford CM, Desai AA, Janisch L, et al A phase I trial to determine the safety, tolerability, and maximum tolerated dose of deforolimus in patients with advanced malignancies. Clin Cancer Res 2009;15:1428–1434.
   PubMed Web of Science ®Google Scholar
• Dancey JE. mTOR inhibitors in hematologic malignancies. Clin Adv Hematol Oncol 2003;1:419–423.
   PubMedGoogle Scholar
• Hess G, Herbrecht R, Romaguera J, et al Phase III study to evaluate temsirolimus compared with investigator's choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol 2009;27:3822–3829.
   PubMed Web of Science ®Google Scholar
• Schmelzle T, Hall MN. TOR, a central controller of cell growth. Cell 2000;103:253–262.
   PubMed Web of Science ®Google Scholar
• Sarbassov DD, Ali SM, Sabatini DM. Growing roles for the mTOR pathway. Curr Opin Cell Biol 2005;17:596–603.
   PubMed Web of Science ®Google Scholar
• Loewith R, Jacinto E, Wullschleger S, et al Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 2002;10:457–468.
   PubMed Web of Science ®Google Scholar
• Sabatini DM, Erdjument-Bromage H, Lui M, Tempst P, Snyder SH. RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell 1994;78:35–43.
   PubMed Web of Science ®Google Scholar
• Brown EJ, Albers MW, Shin TB, et al A mammalian protein targeted by G1-arresting rapamycin-receptor complex. Nature 1994;369:756–758.
   PubMed Web of Science ®Google Scholar
• Sabers CJ, Martin MM, Brunn GJ, et al Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells. J Biol Chem 1995;270:815–822.
   PubMed Web of Science ®Google Scholar
• Shiloh Y. ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer 2003;3:155–168.
   PubMed Web of Science ®Google Scholar
• Drakos E, Rassidakis GZ, Medeiros LJ. Mammalian target of rapamycin (mTOR) pathway signalling in lymphomas. Expert Rev Mol Med 2008;10:1–21.
   Google Scholar
• Beevers CS, Chen L, Liu L, Luo Y, Webster NJ, Huang S. Curcumin disrupts the mammalian target of rapamycin-raptor complex. Cancer Res 2009;69:1000–1008.
   PubMed Web of Science ®Google Scholar
• Averous J, Proud CG. When translation meets transformation: the mTOR story. Oncogene 2006;25:6423–6435.
   PubMed Web of Science ®Google Scholar
• Hudson CC, Liu M, Chiang GG, et al Regulation of hypoxia-inducible factor 1α expression and function by the mammalian target of rapamycin. Mol Cell Biol 2002;22:7004–7014.
   PubMed Web of Science ®Google Scholar
• Del Bufalo D, Ciuffreda L, Trisciuoglio D, et al Antiangiogenic potential of the mammalian target of rapamycin inhibitor temsirolimus. Cancer Res 2006;66:5549–5554.
   PubMed Web of Science ®Google Scholar
• Lane HA, Wood JM, McSheehy PM, et al mTOR inhibitor RAD001 (everolimus) has antiangiogenic/vascular properties distinct from a VEGFR tyrosine kinase inhibitor. Clin Cancer Res 2009;15:1612–1622.
   PubMed Web of Science ®Google Scholar
• Sarbassov DD, Ali SM, Kim DH, et al Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 2004;14:1296–1302.
   PubMed Web of Science ®Google Scholar
• Witzig TE, Kaufmann SH. Inhibition of the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway in hematologic malignancies. Curr Treat Options Oncol 2006;7:285–294.
   PubMedGoogle Scholar
• Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 2006;441:424–430.
   PubMed Web of Science ®Google Scholar
• Long X, Ortiz-Vega S, Lin Y, Avruch J. Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency. J Biol Chem 2005;280:23433–23436.
   PubMed Web of Science ®Google Scholar
• Costa LJ. Aspects of mTOR biology and the use of mTOR inhibitors in non-Hodgkin lymphoma. Cancer Treat Rev 2007;33:78–84.
   PubMed Web of Science ®Google Scholar
• Rudelius M, Pittaluga S, Nishizuka S, et al Constitutive activation of Akt contributes to the pathogenesis and survival of mantle cell lymphoma. Blood 2006;108:1668–1676.
   PubMed Web of Science ®Google Scholar
• Peponi E, Drakos E, Reyes G, Leventaki V, Rassidakis GZ, Medeiros LJ. Activation of mammalian target of rapamycin signaling promotes cell cycle progression and protects cells from apoptosis in mantle cell lymphoma. Am J Pathol 2006;169:2171–2180.
   PubMed Web of Science ®Google Scholar
• Hipp S, Ringshausen I, Oelsner M, Bogner C, Peschel C, Decker T. Inhibition of the mammalian target of rapamycin and the induction of cell cycle arrest in mantle cell lymphoma cells. Haematologica 2005;90:1433–1434.
   PubMed Web of Science ®Google Scholar
• Haritunians T, Mori A, O'Kelly J, Luong QT, Giles FJ, Koeffler HP. Antiproliferative activity of RAD001 (everolimus) as a single agent and combined with other agents in mantle cell lymphoma. Leukemia 2007;21:333–339.
   PubMed Web of Science ®Google Scholar
• Wendel HG, Malina A, Zhao Z, et al Determinants of sensitivity and resistance to rapamycin-chemotherapy drug combinations in vivo. Cancer Res 2006;66:7639–7646.
   PubMed Web of Science ®Google Scholar
• Drakos E, Atsaves V, Li J, et al Stabilization and activation of p53 downregulates mTOR signaling through AMPK in mantle cell lymphoma. Leukemia 2009;23:784–790.
   PubMed Web of Science ®Google Scholar
• Rimokh R, Berger F, Bastard C, et al Rearrangement of CCND1 (BCL1/PRAD1) 3′ untranslated region in mantle-cell lymphomas and t(11q13)-associated leukemias. Blood 1994;83:3689–3696.
   PubMed Web of Science ®Google Scholar
• Dal Col J, Zancai P, Terrin L, et al Distinct functional significance of Akt and mTOR constitutive activation in mantle cell lymphoma. Blood 2008;111:5142–5151.
   PubMed Web of Science ®Google Scholar
• Dal Col J, Dolcetti R. GSK-3β inhibition: at the crossroad between Akt and mTOR constitutive activation to enhance cyclin D1 protein stability in mantle cell lymphoma. Cell Cycle 2008;7:2813–2816.
   PubMed Web of Science ®Google Scholar
• Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005;307:1098–1101.
   PubMed Web of Science ®Google Scholar
• Chiarini F, Fala F, Ricci F, et al PI-103, a dual inhibitor of class IA phosphatidylinositol 3-kinase and mammalian target of rapamycin, has cytotoxic activity in T-cell acute lymphoblastic leukemia cells: a new therapeutic strategy in T-cell acute lymphoblastic leukemia [abstract 1921]. Presented at: 50th ASH Annual Meeting and Exposition; San Francisco, CA: December 6–9, 2008. Blood 2008;112: (Abstract 1921)
   Google Scholar
• Baumann P, Mandl-Weber S, Oduncu F, Schmidmaier R. The novel orally bioavailable inhibitor of phosphoinositol-3-kinase and mammalian target of rapamycin, NVP-BEZ235, inhibits growth and proliferation in multiple myeloma. Exp Cell Res 2009;315:485–497.
   PubMed Web of Science ®Google Scholar
• Zeng Z, Sarbassov dD, Samudio IJ, et al Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML. Blood 2007;109:3509–3512.
   PubMed Web of Science ®Google Scholar
• Choo AY, Blenis J, Not all substrates are treated equally: implications for mTOR, rapamycin-resistance and cancer therapy. Cell Cycle 2009;8:567–572.
   PubMed Web of Science ®Google Scholar
• Farag SS, Zhang S, Miller M, et al Phase II trial of temsirolimus (CCI-779) in patients with relapsed or refractory multiple myeloma (MM): Preliminary results. J Clin Oncol 2006;24: (Abstract 7616).
   Google Scholar
• Witzig TE, Geyer SM, Ghobrial I, et al Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol 2005;23:5347–5356.
   PubMed Web of Science ®Google Scholar
• Ansell SM, Inwards DJ, Rowland KM Jr., et al Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma: a phase 2 trial in the North Central Cancer Treatment Group. Cancer 2008;113:508–514.
   PubMed Web of Science ®Google Scholar
• Smith SM, Pro B, Cisneros A, et al Activity of single agent temsirolimus (CCI-779) in non-mantle cell non-Hodgkin lymphoma subtypes. J Clin Oncol, 2008 ASCO Annual Meeting Proceedings 2008;26 (May 20 suppl): (Abstract 8514).
   Google Scholar
• Yee KW, Zeng Z, Konopleva M, et al Phase I/II study of the mammalian target of rapamycin inhibitor everolimus (RAD001) in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res 2006;12:5165–5173.
   PubMed Web of Science ®Google Scholar
• Johnston PB, Ansell SM, Colgan JP, et al Phase II trial of the oral mTOR inhibitor everolimus (RAD001) for patients with relapsed or refractory lymphoma. J Clin Oncol, 2007 ASCO Annual Meeting Proceedings Part I 2007;25: (Abstract 8055).
   Google Scholar
• Reeder CB, Gornet MK, Habermann TM. A phase II trial of the oral mTOR inhibitor everolimus (RAD001) in relapsed aggressive non-Hodgkin lymphoma (NHL). Blood 2007;110: (Abstract 121).
   Web of Science ®Google Scholar
• Ghobrial IM, Chuma S, Sam A, et al Phase II trial of the mTOR inhibitor RAD001 in relapsed and/or refractory Waldenstrom macroglobulinemia: the Dana Farber Cancer Institute experience [abstract 1011]. Presented at: 50th ASH Annual Meeting and Exposition; San Francisco, CA December 6–9, 2008. Blood 2008;112: (Abstract 1011).
   Google Scholar
• Rizzieri DA, Feldman E, Dipersio JF, et al A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res 2008;14:2756–2762.
   PubMed Web of Science ®Google Scholar
• Zhou Y, Wang H, Fang W, et al Incidence trends of mantle cell lymphoma in the United States between 1992 and 2004. Cancer 2008;113:791–798.
   PubMed Web of Science ®Google Scholar
• Witzig TE. Current treatment approaches for mantle-cell lymphoma. J Clin Oncol 2005;23:6409–6414.
   PubMed Web of Science ®Google Scholar
• Fisher RI, Bernstein SH, Kahl BS, et al Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol 2006;24:4867–4874.
   PubMed Web of Science ®Google Scholar
• Goy A, Bernstein SH, Kahl BS, et al Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study. Ann Oncol 2009;20:520–525.
   PubMed Web of Science ®Google Scholar
• Habermann TM, Lossos IS, Justice G, et al Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma. Br J Haematol 2009;145:344–349.
   PubMed Web of Science ®Google Scholar
• Wiernik PH, Lossos IS, Tuscano JM, et al Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin lymphoma. J Clin Oncol 2008;26:4952–4957.
   PubMed Web of Science ®Google Scholar
• Decker T, Sandherr M, Goetze K, Oelsner M, Ringshausen I, Peschel C. A pilot trial of the mTOR (mammalian target of rapamycin) inhibitor RAD001 in patients with advanced B-CLL. Ann Hematol 2009;88:221–227.
   PubMed Web of Science ®Google Scholar
• Witzig E, Habermann T, Reeder C, et al A phase II trial of the oral mTOR inhibitor everolimas in relapsed non-Hodgkin lymphoma (NHL) and Hodgkin disease (HD) [abstract 1081]. Presented at: 14th Congress of the European Hematology Association; Berlin, Germany June 4–7 2009. Haematologica 2009;94(Suppl 2): (Abstract 1081).
   Google Scholar
• Crazzolara R, Cisterne A, Thien M, et al Potentiating effects of RAD001 (everolimus) on vincristine therapy in childhood acute lymphoblastic leukemia. Blood 2009;113:3297–3306.
   PubMed Web of Science ®Google Scholar
• Decker T. Is mTOR inhibition a therapeutic option in chronic lymphocytic leukemia?. Leuk Lymphoma 2008;49:2235–2236.
   PubMed Web of Science ®Google Scholar
• Aleskog A, Norberg M, Nygren P, et al Rapamycin shows anticancer activity in primary chronic lymphocytic leukemia cells in vitro, as single agent and in drug combination. Leuk Lymphoma 2008;49:2333–2343.
   PubMed Web of Science ®Google Scholar
• Teachey DT, Greiner R, Seif A, et al Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome. Br J Haematol 2009;145:101–106.
   PubMed Web of Science ®Google Scholar
• Rheingold SR, Sacks N, Chang YJ, et al A phase I trial of sirolimus (rapamycin) in pediatric patients with relapsed/refractory leukemia [abstract]. Blood 2007;110: (Abstract 2834).
   Web of Science ®Google Scholar
• Pulsipher M, Wall D, Goyal R, Grupp S, Bunin N. Sirolimus (SRL)-based GVHD prophylaxis after TBI/TT/CY allogeneic HSCT in pediatric patients with HR ALL: results of a multi-institutional pilot study [abstract]. Biol Blood Marrow Transplant 2008;14(Suppl 2 part 1): 28.
   PubMed Web of Science ®Google Scholar
• Shi Y, Hsu JH, Hu L, Gera J, Lichtenstein A. Signal pathways involved in activation of p70S6K and phosphorylation of 4E-BP1 following exposure of multiple myeloma tumor cells to interleukin-6. J Biol Chem 2002;277:15712–15720.
   PubMed Web of Science ®Google Scholar
• Hu L, Shi Y, Hsu JH, Gera J, Van NB, Lichtenstein A. Downstream effectors of oncogenic ras in multiple myeloma cells. Blood 2003;101:3126–3135.
   PubMed Web of Science ®Google Scholar
• Yan H, Frost P, Shi Y, et al Mechanism by which mammalian target of rapamycin inhibitors sensitize multiple myeloma cells to dexamethasone-induced apoptosis. Cancer Res 2006;66:2305–2313.
   PubMed Web of Science ®Google Scholar
• Frost P, Shi Y, Hoang B, Lichtenstein A. AKT activity regulates the ability of mTOR inhibitors to prevent angiogenesis and VEGF expression in multiple myeloma cells. Oncogene 2007;26:2255–2262.
   PubMed Web of Science ®Google Scholar
• Frost P, Shi Y, Hoang B, Gera J, Lichtenstein A. Regulation of D-cyclin translation inhibition in myeloma cells treated with mammalian target of rapamycin inhibitors: rationale for combined treatment with extracellular signal-regulated kinase inhibitors and rapamycin. Mol Cancer Ther 2009;8:83–93.
   PubMed Web of Science ®Google Scholar
• Ghobrial IM, Munshi N, Schlossman R, et al Phase I trial of CCI-779 (temsirolimus) and weekly bortezomib in relapsed and/or refractory multiple myeloma [abstract 3696]. Presented at: 50th ASH Annual Meeting and Exposition; San Francisco, CA December 6–9, 2008. Blood 2008;112: (Abstract 3696).
   Google Scholar
• Recher C, Beyne-Rauzy O, Demur C, et al Antileukemic activity of rapamycin in acute myeloid leukemia. Blood 2005;105:2527–2534.
   PubMed Web of Science ®Google Scholar
• Yee KW, Garcia-Manero G, Thomas D, et al A phase II study of temsirolimus (CCI-779) in patients with advanced leukemias. Blood 2004;104: 214b (Abstract 4523).
   Web of Science ®Google Scholar
• Ly C, Arechiga AF, Melo JV, Walsh CM, Ong ST. Bcr-Abl kinase modulates the translation regulators ribosomal protein S6 and 4E-BP1 in chronic myelogenous leukemia cells via the mammalian target of rapamycin. Cancer Res 2003;63:5716–5722.
   PubMed Web of Science ®Google Scholar
• Sillaber C, Mayerhofer M, Bohm A, et al Evaluation of antileukaemic effects of rapamycin in patients with imatinib-resistant chronic myeloid leukaemia. Eur J Clin Invest 2008;38:43–52.
   PubMed Web of Science ®Google Scholar