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TRAIL resistance results in cancer progression: a TRAIL to perdition?

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Abstract

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL, APO-2L) is a mediator of cell death that preferentially targets cancer cells. The potential of TRAIL as a chemotherapeutic agent is limited, however, because of the emergence of TRAIL resistance. Furthermore, recent studies have demonstrated that alternative TRAIL signaling is unmasked in TRAIL resistant cells. In these cells, the predominant effect of TRAIL receptor activation is the activation of nuclear factor-κB (NF-κB), which promotes tumor metastases and invasion. TRAIL resistance can occur at the level of the death inducing signaling complex via upregulation of cFLIP or via an increase in antiapoptotic proteins of the Bcl-2 family. A paradigm emerges from this information, that chemotherapy, targeting NF-κB, cFLIP, or antiapoptotic proteins of the Bcl-2 family, in combination with TRAIL maybe more rational than TRAIL therapy alone.

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References

  • Ashkenazi A, Dixit VM . (1999). Curr Opin Cell Biol 11: 255–260.

  • Bardeesy N, DePinho RA . (2002). Nat Rev Cancer 2: 897–909.

  • Budd RC, Yeh WC, Tschopp J . Nat Rev Immunol 6: 196–204.

  • Degli-Esposti MA, Dougall WC, Smolak PJ, Waugh JY, Smith CA, Goodwin RG . (1997). Immunity 7: 813–820.

  • Galligan L, Longley DB, McEwan M, Wilson TR, McLaughlin K, Johnston PG . (2005). Mol Cancer Ther 4: 2026–2036.

  • Ishimura N, Isomoto H, Bronk SF, Gores GJ . (2006). Am J Physiol Gastrointest Liver Physiol 290: G129–G136.

  • Kim Y, Suh N, Sporn M, Reed JC . (2002). J Biol Chem 277: 22320–22329.

  • Kimberley FC, Screaton GR . (2004). Cell Res 14: 359–372.

  • Luo JL, Maeda S, Hsu LC, Yagita H, Karin M . (2004). Cancer Cell 6: 297–305.

  • Okano H, Shiraki K, Inoue H, Kawakita T, Yamanaka T, Deguchi M et al. (2003). Lab Invest 83: 1033–1043.

  • Peter ME, Legembre P, Barnhart BC . (2005). Biochim Biophys Acta 1755: 25–36.

  • Sayers TJ, Murphy WJ . (2006). Cancer Immunol Immunother 55: 76–84.

  • Taniai M, Grambihler A, Higuchi H, Werneburg N, Bronk SF, Farrugia DJ et al. (2004). Cancer Res 64: 3517–3524.

  • Trauzold A, Siegmund D, Schniewind B, Sipos B, Egberts J, Zorenkov D et al. (2006). Oncogene (in press).

  • Truneh A, Sharma S, Silverman C, Khandekar S, Reddy MP, Deen KC et al. (2000). J Biol Chem 275: 23319–23325.

  • Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK et al. (1995). Immunity 3: 673–682.

  • Zhang L, Fang B . (2005). Cancer Gene Ther 12: 228–237.

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  1. Division of Gastroenterology and Hepatology, Miles and Shirley Fiterman Center in Digestive Diseases, Mayo Clinic College of Medicine, Rochester, MN, USA

    H Malhi & G J Gores

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  1. H Malhi
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  2. G J Gores
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Correspondence to G J Gores.

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Malhi, H., Gores, G. TRAIL resistance results in cancer progression: a TRAIL to perdition?. Oncogene 25, 7333–7335 (2006). https://doi.org/10.1038/sj.onc.1209765

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