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Review

Mechanisms of mammalian target of rapamycin inhibition in sarcoma: present and future

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Pages 1145-1154 | Published online: 10 Jan 2014

References

  • Brown EJ, Albers MW, Shin TB et al. A mammalian protein targeted by G1-arresting rapamycin-receptor complex. Nature369, 756–758 (1994).
  • Chiu MI, Katz H, Berlin V. RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex. Proc. Natl Acad. Sci. USA91, 12574–12578 (1994).
  • Sabatini DM, Erdjument-Bromage H, Lui M et al. RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell78, 35–43 (1994).
  • Heitman J, Movva NR, Hall MN. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science253, 905–909 (1991).
  • Kotilingam D, Lev DC, Lazar AJF, Pollock RE. Staging soft-tissue sarcoma: evolution and change. CA Cancer J. Clin.56, 282–229 (2006).
  • Jemal A, Siegel R, Ward E et al. Cancer statistics, 2007. CA Cancer J. Clin.57, 43–66 (2007).
  • Borden EC, Baker LH, Bell RS et al. Soft tissue sarcomas of adults: state of the translational science. Clin. Can. Res.9, 1941–1956 (2003).
  • Henley ML, Maki RG, Venkatraman E et al. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a Phase II trial. J. Clin. Oncol.20, 2824–2831 (2002).
  • Bay J-O, Ray-Coquard I, Fayette J et al. Docetaxel and gemcitabine combination in 133 advanced soft-tissue sarcoman: a retrospective analysis. Int. J. Cancer119, 706–711 (2006).
  • van Oosterom AT, Judson I, Verweij J et al. Safety and efficacy of imatinib (ST1571) in metastatic gastrointestinal stromal tumors: a Phase I study. Lancet358, 1421–1423 (2001).
  • Verweij J, Casali PG, Zalcberg J et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomixed trial. Lancet364, 1127 (2004).
  • Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev.18, 1926–1945 (2004).
  • Peterson RT, Beal PA, Comb MJ, Schreiber SL. FKBP12-rapamycin-associated protein (FRAP) autophosphorylates at serine 2481 under translationally repressive conditions. J. Biol. Chem.275, 7416–7423 (2000).
  • Takahashi T, Hara K, Inoue H et al. Carboxyl-terminal region conserved among phosphoinositide-kinase-related kinases is indispensable for mTOR function in vivo and in vitro. Genes Cells5, 765–775 (2000).
  • Brunn GJ, Hudson CC, Sekulic A et al. Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin. Science277, 99–101 (1997).
  • Burnett PE, Barrow RK, Cohen NA, Snyder SH, Sabatini DM. RAFT1 phosphorylation of the translational regulators p70S6 kinase and 4E-BP1. Proc. Natl. Acad. Sci. USA95, 1432–1437 (1998).
  • Inoki K, Corradetti MN, Guan KL. Dysregulation of the TSC-mTOR pathway in human disease. Nat. Genet.37(1), 19–24 (2005).
  • Ali IU, Schriml LM, Dean M. Mutational spectra of PTEN/MMAC1 gene: a tumor suppressor with lipid phosphatase activity. J. Natl Cancer Inst.91, 1922–1932 (1999).
  • Manning BD, Cantley LC. Rheb fills a GAP between TSC and TOR. Trends Biochem. Sci.28, 573–576 (2003).
  • Goncharova EA, Goncharova DA, Eszterhas A et al. Tuberin regulates p70 S6 kinase activation and ribosomal protein S6 phosphorylation. J. Biol. Chem.277, 30958–30967 (2002).
  • Kwiatkowski DJ, Zhang H, Bandura JL et al. A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in TSC1 null cells. Hum. Mol. Genet.11, 525–534 (2002).
  • 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. USA98, 10320–10325 (2001).
  • Corradetti MN, Inoki K, Bardeesy N et al. Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and the Peutz–Jeghers syndrome. Genes Dev.18, 1533–1538 (2004).
  • Shaw RJ, Bardeesi N, Manning BD et al. The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell6, 91–99 (2004).
  • Hara K, Maruki Y, Long X et al. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell110, 177–189 (2002).
  • Kim DH, Sarbassov DD, Ali SM et al. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell110, 163–175 (2002).
  • Dutcher JP. Mammalian target of rapamycin inhibition. Clin. Cancer Res.10, 6382–6387 (2004).
  • Foster DA. Regulation fo mTOR by phosphatidic acid? Cancer Res.67, 1–4 (2007).
  • Fang Y, Vilella-Bach M, Bachmann R et al. Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science294, 1942–1945 (2001).
  • Chen Y, Roderik V, Foster FA. Alternative phospholipase D/mTOR survival signal in human breast cancer cells. Oncogene24, 672–979 (2005).
  • Douros J, Suffness M. New antitumor substances of natural origin. Cancer Treat. Rev.8, 63–87 (1981).
  • Dilling MB, Dias P, Shapiro DN et al. Rapamycin selectively inhibits the growth of childhood rhabdomyosarcoma cells through inhibition of signaling via the type I insulin-like growth factor receptor. Cancer Res.54, 903–907 (1994).
  • Dancey JE. Therapeutic targets: mTOR and related pathways. Cancer Biol. Ther.5(9), 1065–1073 (2006).
  • Decker T, Hipp S, Ringshausen I et al. Rapamycin-induced G1 arrest in cycling B-CLL cells is associated with reduced expression of cyclin D3, cyclin E, cyclin A and surviving. Blood101, 278–285 (2003).
  • Luo Y, Marx SO, Kiyokawa H et al. Rapamycin resistance tied to defective regulation of p27Kip1. Mo.l Cell Biol.16, 6744–6751 (1996).
  • Okuno S. Mammalian target of rapamycin inhibitors in sarcomas. Curr. Opin. Oncol.18, 360–362 (2006).
  • Schuetze SM, Baker LH, Maki RG. Sirolimus reduced tumor-related morbidity and resulted in biochemical and radiographic response in patients with progressive sarcoma. Proc. Am. Soc. Clin. Oncol.24, A9503 (2006).
  • Raymond E, Alexandre J, Faivre S et al. Safety and pharmacokinetics of escalated doses of weekly intravenous infusion of CCI-779, a novel mTOR inhibitor, in patients with cancer. J. Clin. Oncol.22, 2336–2347 (2004).
  • Peralba JM, deGraffenried L, Friedrichs W et al. Pharmacodynamic evaluation of CCI-779, an inhibitor of mTOR, in cancer patients. Clin. Cancer Res.9, 2887–2892 (2003).
  • Hidalgo M, Rowinsky E, Erlichman C et al. A Phase I and pharmacological study of CCI-779, a rapamycin ester cell cycle inhibitor. Ann. Oncol.11, 133 (2000) (Abstract 606O).
  • Hidalgo M, Rowinsky E, Erlichman C et al. Phase I and pharmacological study of CCI-779, a cell cycle inhibitor. Proceedings of the 11th NCI-EORTC-AACR Symposium on New Drugs in Cancer Therapy. Clin. Can. Res.6, A413 (2000).
  • Hidalgo M, Buckner JC, Erlichman C et al. A Phase I and pharmacokinetic study of temsirolimus (CCI-779) administered intravenously daily for 5 days every 2 weeks to patients with advanced cancer. Clin. Cancer Res.12(19), 5755–5763 (2006).
  • Chang SM, Kuhn J, Wen P et al. Phase I/pharmacokinetic study of CCI-779 in patients with recurrent malignant glioma on enzyme-inducing antiepileptic drugs. Invest. New Drugs22, 427–435 (2004).
  • Okuno SH, Mahoney MR, Bailey HH et al. A multicenter Phase 2 consortium (P2C) study of the mTOR inhibitor CCI-779 in advanced soft tissue sarcomas (STS). Proc. Am. Soc. Clin. Oncol.24, A9504 (2006).
  • O’Donnell A, Faivre S, Judson I et al. A Phase I study of the oral mTOR inhibitor RAD001 as monotherapy to identify the optimal biologically effective dose using toxicity, pharmacokinetic (PK) and pharmacodynamic (PD) endpoints in patients with solid tumors. Proc. Am. Soc. Clin. Oncol.22, A803 (2003).
  • Tabernero J, Rojo F, Burris E et al. A Phase I study with tumor molecular pharmacodynamic (MPD) evaluation of dose and schedule of the oral mTOR-inhibitor everolimus (RAD001) in patients with advanced solid tumors. Proc. Am. Soc. Clin. Oncol.24, A3007 (2005).
  • Mita MM, Rowinsky EK, Mita AC et al. Phase I, pharmacokinetic (PK) and pharmacodynamic (PD) study of AP23573, an mTOR inhibitor, administered IV daily × 5 every other week in patients (pts) with refractory or advanced malignancies. Proc. Am. Soc. Clin. Oncol.23, 3076 (2004).
  • Desai AA, Janisch L, Berk LR et al. A Phase I trail of a novel mTOR inhibitor AP23573 administered weekly (wkly) in patients (pts) with refaractory or advanced malignancies: a pharmacokinetic (PK) and pharmacodynamic (PD) analysis. Proc. Am. Soc. Clin. Oncol.23, A3150 (2004).
  • Chawla SP, Tolcher AW, Staddon AP et al. Updated results of a Phase II trial of AP23573, a novel mTOR inhibitor, in patients (pts) with advanced soft tissue or bone sarcomas. Proc. Am. Soc. Clin. Oncol.24, A9505 (2006).
  • Sankhala KK, Chawla SP, Iagaru A et al. Early response evaluation of therapy with AP23573 (an mTOR inhibitor) in sarcoma using [18F]2-fluro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan. Proc. Am. Soc. Clin. Oncol.23, A9028 (2005).
  • Van Oosterom AT, Dumez H, Desai J et al. Combination signal transduction inhibition: a Phase I/II trial of the oral mTOR-inhibitor everolimus (E, RAD001) and imatinib mesylate (IM) in patients (pts) with gastrointestinal stromal tumor (GIST) refractory to IM. Proc. Am. Soc. Clin. Oncol.22, A3002 (2004).
  • Faivre S, Kroemer G, Raymond E. Current development of mTOR inhibitors as anticancer agents. Nat. Rev.5, 671–682 (2006).
  • von Mehren M. New therapeutics for soft-tissue sarcomas in adults. Oncology21(1), 123–126 (2007).
  • Buck E, Eyzaguirre A, Brown E et al. Rapamycin synergizes with the epidermal growth factor receptor erlotinib in non-small-cell lung, pancreatic, colon and breast tumors. Mol. Cancer Ther.5(11), 2676–2684 (2006).
  • Ikezoe T, Nishioka C, Tasaka T et al. The antitumor effects of sunitinib (formerly SU11248) against a variety of human hematologic malignancies: enhancement of growth inhibition via inhibition of mammalian target of rapamycin signaling. Mol. Cancer Ther.5(10), 2522–2530 (2006).

Website

  • Fouladi M. Phase I/II trial of RAD001 (everolimus) in pediatric patients with recurrent refractory solid tumors or brain tumors with Phase II limited to recurrent or refractory rhabdomyosarcomas and non rhabdomyosarcomatous soft tissue sarcomas. ClinicalTrials.gov identifier NCT00187174 http://clinicaltrials.gov/ct/show/NCT00187174

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