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  • Title: Potential and caveats of TRAIL in cancer therapy.
    Author: Held J, Schulze-Osthoff K.
    Journal: Drug Resist Updat; 2001 Aug; 4(4):243-52. PubMed ID: 11991679.
    Abstract:
    Induction of apoptosis in tumor cells is a major goal for chemotherapy and radiation treatment strategies. However, disordered gene expression often leads to apoptosis resistance rendering tumor cells insensitive to various conventional treatments. TNF-related apoptosis-inducing ligand (TRAIL) is a recently identified cytokine of the TNF superfamily that induces apoptosis in tumor cells upon binding to different receptors. Remarkably, the majority of tumor cell lines are sensitive to TRAIL-induced apoptosis, while most nontransformed cell types are TRAIL-resistant. Furthermore, a combination treatment of TRAIL with ionizing irradiation or chemotherapeutic agents induces apoptosis in a highly synergistic manner, particularly in those cells that are otherwise resistant to a sole treatment. In contrast to other TNF members, TRAIL apparently does not exert overt systemic toxicity in murine and primate models, although unexpected concerns about a potential hepatotoxicity of TRAIL have been recently raised. While the molecular mechanisms of TRAIL sensitivity and resistance are poorly understood, TRAIL seems to be a promising biological agent for combination therapy with chemotherapeutic drugs or irradiation.
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