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Merck

TRAIL and cancer therapy.

Cancer letters (2008-03-11)
Frank A E Kruyt
RESUMEN

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors are promising targets for the selective eradication of tumor cells while sparing normal cells. Currently, both recombinant TRAIL proteins and TRAIL receptor agonistic antibodies are being tested in the clinic, showing encouraging antitumor activities and mild side effects. Unfortunately, resistance to TRAIL therapy is frequently encountered requiring combined treatments with sensitizing agents. Standard chemotherapeutics can enhance TRAIL sensitivity; however, more specific and less toxic agents are needed to exploit the full antitumor potential of TRAIL. Here, a brief overview of the TRAIL signaling pathway is given together with a short description of early results obtained with TRAIL therapy in the clinic. Mechanisms of TRAIL resistance and ways to overcome these by targeted agents that either neutralize apoptotic blockades or suppress prosurvival signals also triggered by TRAIL are highlighted, such as inhibitors of IAPs, Bcl-2 family members, HDACi, and modulators of NF-kappaB, Raf and EGFR signaling.

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Sigma-Aldrich
TRAIL Protein, Recombinant human, Human TRAIL (TNF-Related Apoptosis Inducing Ligand), also called APO2 Ligand, is a cytotoxic protein which activates rapid apoptosis in tumor cells, but not in normal cells.