Onkologie. 2010:4(3):185-188

New mechanism of action in the treatment of renal cell carcinoma: m-TOR - a novel target

Hana Študentová1, Bohuslav Melichar1,2
1 Onkologická klinika, FN a LF UP Olomouc
2 Klinika onkologie a radioterapie, FN Hradec Králové

PI3K/Akt/mTOR is a crucial signal transduction pathway taking part in the process of cancerogenesis as well as a target for anticancer

therapy. Inhibition of this pathway has become a promising target for cancer research, since alterations at distinct points of this signal

transduction pathway have been observed in multiple cancer types. HIF-alpha over-expression, typical for renal cell carcinoma, leads to

accumulation of proangiogenic factors and angiogenesis induction. Currently, there are 2 approaches of anticancer management using

different mechanisms of action: anti-VEGF (R) therapy, targeting mostly tumour angiogenesis, and mTOR inhibitors that exhibit a direct

anti-tumour effect leading to cell cycle arrest in G1 phase and apoptosis induction.

Keywords: mTOR, mTOR inhibition, HIF-alpha, VEGF (R) targeted therapy

Published: July 1, 2010  Show citation

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Študentová H, Melichar B. New mechanism of action in the treatment of renal cell carcinoma: m-TOR - a novel target. Onkologie. 2010;4(3):185-188.
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References

  1. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004; 18(16): 1926-1945. Go to original source... Go to PubMed...
  2. Noh WC, Mondesire WH, Peng J, et al. Determinants of rapamycin sensitivity in breast cancer cells. Clin Cancer Res 2004; 10(3): 249-258. Go to original source... Go to PubMed...
  3. Oshiro N, Yoshino K, Hidaya S, et al. Dissociation of raptro from mTOR is a mechanism of ramapycin-induced inhibition of mTOR function. Genes Cells 2004; 9(4): 359-366. Go to original source... Go to PubMed...
  4. Kim WY, Kaelin WG. Role of VHL gene mutation in human cancer. J Clin Oncol 2004; 22: 4991-5004. Go to original source... Go to PubMed...
  5. Kondo K, Yao M, Yoshida M, et al. Comprehensive mutanional analysis of the VHL gene in sporadic renal cell carcinoma: Relationship to clinicopathological parametres. Genes Chromosomes Cancer 2002; 34: 58-68. Go to original source... Go to PubMed...
  6. Rini BI. Metastatic Renal Cell Carcinoma: Many treatment options, One Patient. J Clin Oncol 2009; 19: 3225-3234. Go to original source... Go to PubMed...
  7. Brugarolas JB, Vazquez F, Reddy A, Sellers WR, Kaelin WG Jr. TSC2 regulates VEGF through mTOR-dependent and independent pathways. Cancer Cell 2003; 4: 147-158. Go to original source... Go to PubMed...
  8. Thomas GV, Tran C, Mellinghoff IK, et al. Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer. Nat Med 2006; 12: 122-127. Go to original source... Go to PubMed...
  9. Bergers G, Hanahan D. Modes of resistance to ani-angiogenic therapy. Nature 2008: 592-603. Go to original source... Go to PubMed...
  10. Meric-Bernstam F, Gonzales-Angulo AM. Targeting the mTOR signaling network for cancer therapy. J Clin Oncol 2009; 27: 2278-2287. Go to original source... Go to PubMed...
  11. 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. Go to original source... Go to PubMed...
  12. Edinger AL, Linardic CM, Chiang GG, Thompson CB, Abraham RT. Differential effects of rapamycin on mammalian target of rapamycin signaling functions in mammalian cells. Cancer Res 2003; 63: 8451-8460.
  13. Sarbassov DD, Guertin DA, Ali SM, et al. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005; 307(5712): 1098-1101. Go to original source... Go to PubMed...




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