BibTex RIS Kaynak Göster

mTOR signaling pathway and mTOR inhibitors in the treatment of cancer

Yıl 2013, Cilt: 40 Sayı: 1, 156 - 160, 01.03.2013
https://doi.org/10.5798/diclemedj.0921.2013.01.0248

Öz

Mammalian target of rapamycin (mTOR) plays a major role in the regulation of protein translation, cell growth, and metabolism. Three basic signalling pathways that have been described as important in cancer including the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR kinase cascade, the protein kinase C (PKC) family, and the mito­gen-activated protein kinase (MAPK)/Ras signalling cas­cades. mTOR has been defined as a key kinase acting downstream of the activation of PI3K/AKT. These path­ways are frequently deteriorated in cancer, and therefore mTOR inhibition is a important antitumor target. mTOR inhibitors include rapamycin (i.e. sirolimus) and its deriva­tives; temsirolimus, everolimus, ridaforolimus and defo­rolimus. mTOR inhibitors has the important potential to provide anticancer activity in many tumor types.

Kaynakça

  • Faivre S, Kroemer G, Raymond E. Current development of mTOR inhibitors as anticancer agents. Nat Rev 2006;5:671- 8.
  • Seghal SN, Baker H, Vézina C. Rapamycin (AY-22,989), a new antifungal antiobiotic II. Fermentation, isolation and characterization. J Antibiot 1975; 28:727-2.
  • Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004;18:1926-5.
  • Douros J, Suffnes M. New antitumor substances of natural origin. Cancer Treat Rev 1981; 8:63-7.
  • Atkins MB, Hidalgo M, Stadler WM, et al. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of sirolimus kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol 2004;22:909-8.
  • Motzer RJ, Escudier B, Oudard S, et al. RAD001 vs placebo in patients with metastatic renal cell carcinoma after pro- gression on VEGFr-TKI therapy: results from a random- ized, double blind, multicenter phase-III study [abstract]. J Clin Oncol 2008;26:Abstract LBA5026.
  • Yuan R, Kay A, Berg WJ and Lebwohl D. Targeting tumori- genesis: development and use of mTOR inhibitors in cancer therapy. J Hematol & Oncol 2009; 2:1-12.
  • Wysocki PJ. mTOR in renal cell cancer: modulator of tu- mor biology and therapeutic target. Expert Rev Mol Diagn 2009;9: 231-41.
  • Shaw RJ, Cantley LC. Ras, PI(3)K, and mTOR signalling controls tumor cell growth. Nature 2006; 441:424-30.
  • Vivanco I, Sawyers CL, The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2002;2: 489-01.
  • Bellacosa A, Chan TO, Ahmed NN, et al.Akt activation by growth factors is a multiple-step process: the role of the PH domain. Oncogene 1998;17: 313-25.
  • Hay N. The Akt-mTOR tango and its relevance to cancer. Cancer Cell 2005;8:179-3.
  • Pawson T. Introduction: Protein kinases. FASEB J 1994;8:1112-13.
  • Sancak Y, Thoreen CC, Peterson TR et al. PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol Cell 2007;25: 903-15.
  • Figlin RA, Brown E, Armstrong AJ, et al. NCCN task force report: mTOR inhibition in solid tumors. JNCCN 2008; 6:1-20.
  • Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005;307:1098-01.
  • Zhou H, Huang S. mTOR signaling in cancer cell motility and tumor metastasis. Crit Rev Eukaryot Gene Expr 2010; 20: 1-16.
  • Toschi A, Lee E, Gadir N, Ohh M, Foster DA. Differen- tial dependence of hypoxia- inducible factors 1a and 2a on mTORC1 and mTORC2. J. Biol Chem 2008;283:34495-9.
  • Feng, Z, Zhang, H, Levine, AJ, Jin S. The coordinate regu- lation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci 2005;102: 8204-9.
  • Thomas G, Hall MN. TOR signaling and control of control of cell growth. Curr Opin Cell Biol 1997; 9: 782-7.
  • Schmelzle T, Hall MN. TOR, a central controller of cell growth. Cell 2000;103:253-2.
  • Motzer RJ, Escudier B, Oudard S, et al. RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell car- cinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372:449-56.
  • Yao JC, Phan AT, Chang DZ etal. Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low to inter- mediate-grade neuroendocrine tumors: results of a phase II study. J Clin Oncol 2008;26:4311-18.
  • www.clinicaltrials.gov: Ridaforolimus in treatment of sar- coma - SUCCEED (Sarcoma Multi-Center Clinical Evalu- ation of the Efficacy of Ridaforolimus). (http://www.clini- caltrials.gov/ct2/ show/study/NCT00538239). Accessed Feb 19, 2012.
  • Yekaterina Y. Zaytseva, Joseph D. Valentino, Pat Gulhati, B. Mark Evers. mTOR inhibitors in cancer therapy. Cancer Letters 2012:319:1-7.

Kanser tedavisinde mTOR sinyal yolağı ve mTOR inhibitörleri

Yıl 2013, Cilt: 40 Sayı: 1, 156 - 160, 01.03.2013
https://doi.org/10.5798/diclemedj.0921.2013.01.0248

Öz

mTOR (Rapamisin protein kompleksinin memeli hedefi) hücre büyümesi ve metabolizmasında önemli role sahip­tir. Kanserde önemli olduğu saptanan üç temel sinyalizas­yon yolu; (PI3K)/AKT kinaz zinciri, protein kinaz C ailesi (PKC) ve mitojenle aktive olan protein kinaz (MAPK)/Ras vardır. mTOR; PI3K/AKT sinyal yolağının akış aşağı akti­vasyonunda anahtar bir kinazdır. Bu yolaklar sıklıkla kan­serde bozulur ve bu yüzden de mTOR önemli bir antitü­mör hedeftir. Antikanser ajanlar olarak mTOR inhibitörleri rapamisin ve ondan türetilmiş temsirolimus, everolimus ve ridaforolimus sonradan deforolimus oluşturmaktadır. mTOR inhibitörleri birçok kanser tipinde önemli bir hedef­tir.

Kaynakça

  • Faivre S, Kroemer G, Raymond E. Current development of mTOR inhibitors as anticancer agents. Nat Rev 2006;5:671- 8.
  • Seghal SN, Baker H, Vézina C. Rapamycin (AY-22,989), a new antifungal antiobiotic II. Fermentation, isolation and characterization. J Antibiot 1975; 28:727-2.
  • Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004;18:1926-5.
  • Douros J, Suffnes M. New antitumor substances of natural origin. Cancer Treat Rev 1981; 8:63-7.
  • Atkins MB, Hidalgo M, Stadler WM, et al. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of sirolimus kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol 2004;22:909-8.
  • Motzer RJ, Escudier B, Oudard S, et al. RAD001 vs placebo in patients with metastatic renal cell carcinoma after pro- gression on VEGFr-TKI therapy: results from a random- ized, double blind, multicenter phase-III study [abstract]. J Clin Oncol 2008;26:Abstract LBA5026.
  • Yuan R, Kay A, Berg WJ and Lebwohl D. Targeting tumori- genesis: development and use of mTOR inhibitors in cancer therapy. J Hematol & Oncol 2009; 2:1-12.
  • Wysocki PJ. mTOR in renal cell cancer: modulator of tu- mor biology and therapeutic target. Expert Rev Mol Diagn 2009;9: 231-41.
  • Shaw RJ, Cantley LC. Ras, PI(3)K, and mTOR signalling controls tumor cell growth. Nature 2006; 441:424-30.
  • Vivanco I, Sawyers CL, The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2002;2: 489-01.
  • Bellacosa A, Chan TO, Ahmed NN, et al.Akt activation by growth factors is a multiple-step process: the role of the PH domain. Oncogene 1998;17: 313-25.
  • Hay N. The Akt-mTOR tango and its relevance to cancer. Cancer Cell 2005;8:179-3.
  • Pawson T. Introduction: Protein kinases. FASEB J 1994;8:1112-13.
  • Sancak Y, Thoreen CC, Peterson TR et al. PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol Cell 2007;25: 903-15.
  • Figlin RA, Brown E, Armstrong AJ, et al. NCCN task force report: mTOR inhibition in solid tumors. JNCCN 2008; 6:1-20.
  • Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005;307:1098-01.
  • Zhou H, Huang S. mTOR signaling in cancer cell motility and tumor metastasis. Crit Rev Eukaryot Gene Expr 2010; 20: 1-16.
  • Toschi A, Lee E, Gadir N, Ohh M, Foster DA. Differen- tial dependence of hypoxia- inducible factors 1a and 2a on mTORC1 and mTORC2. J. Biol Chem 2008;283:34495-9.
  • Feng, Z, Zhang, H, Levine, AJ, Jin S. The coordinate regu- lation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci 2005;102: 8204-9.
  • Thomas G, Hall MN. TOR signaling and control of control of cell growth. Curr Opin Cell Biol 1997; 9: 782-7.
  • Schmelzle T, Hall MN. TOR, a central controller of cell growth. Cell 2000;103:253-2.
  • Motzer RJ, Escudier B, Oudard S, et al. RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell car- cinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372:449-56.
  • Yao JC, Phan AT, Chang DZ etal. Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low to inter- mediate-grade neuroendocrine tumors: results of a phase II study. J Clin Oncol 2008;26:4311-18.
  • www.clinicaltrials.gov: Ridaforolimus in treatment of sar- coma - SUCCEED (Sarcoma Multi-Center Clinical Evalu- ation of the Efficacy of Ridaforolimus). (http://www.clini- caltrials.gov/ct2/ show/study/NCT00538239). Accessed Feb 19, 2012.
  • Yekaterina Y. Zaytseva, Joseph D. Valentino, Pat Gulhati, B. Mark Evers. mTOR inhibitors in cancer therapy. Cancer Letters 2012:319:1-7.
Toplam 25 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Derlemeler
Yazarlar

Mehmet Küçüköner Bu kişi benim

Yayımlanma Tarihi 1 Mart 2013
Gönderilme Tarihi 2 Mart 2015
Yayımlandığı Sayı Yıl 2013 Cilt: 40 Sayı: 1

Kaynak Göster

APA Küçüköner, M. (2013). Kanser tedavisinde mTOR sinyal yolağı ve mTOR inhibitörleri. Dicle Medical Journal, 40(1), 156-160. https://doi.org/10.5798/diclemedj.0921.2013.01.0248
AMA Küçüköner M. Kanser tedavisinde mTOR sinyal yolağı ve mTOR inhibitörleri. diclemedj. Mart 2013;40(1):156-160. doi:10.5798/diclemedj.0921.2013.01.0248
Chicago Küçüköner, Mehmet. “Kanser Tedavisinde MTOR Sinyal yolağı Ve MTOR inhibitörleri”. Dicle Medical Journal 40, sy. 1 (Mart 2013): 156-60. https://doi.org/10.5798/diclemedj.0921.2013.01.0248.
EndNote Küçüköner M (01 Mart 2013) Kanser tedavisinde mTOR sinyal yolağı ve mTOR inhibitörleri. Dicle Medical Journal 40 1 156–160.
IEEE M. Küçüköner, “Kanser tedavisinde mTOR sinyal yolağı ve mTOR inhibitörleri”, diclemedj, c. 40, sy. 1, ss. 156–160, 2013, doi: 10.5798/diclemedj.0921.2013.01.0248.
ISNAD Küçüköner, Mehmet. “Kanser Tedavisinde MTOR Sinyal yolağı Ve MTOR inhibitörleri”. Dicle Medical Journal 40/1 (Mart 2013), 156-160. https://doi.org/10.5798/diclemedj.0921.2013.01.0248.
JAMA Küçüköner M. Kanser tedavisinde mTOR sinyal yolağı ve mTOR inhibitörleri. diclemedj. 2013;40:156–160.
MLA Küçüköner, Mehmet. “Kanser Tedavisinde MTOR Sinyal yolağı Ve MTOR inhibitörleri”. Dicle Medical Journal, c. 40, sy. 1, 2013, ss. 156-60, doi:10.5798/diclemedj.0921.2013.01.0248.
Vancouver Küçüköner M. Kanser tedavisinde mTOR sinyal yolağı ve mTOR inhibitörleri. diclemedj. 2013;40(1):156-60.