Targeting the Apo2L/TRAIL system for the therapy of autoimmune diseases and cancer.

Abstract:

:Apo 2 ligand/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL), is a member of the TNF family of cytokines, which can induce apoptotic cell death in cells expressing at least one of their specific death receptors, DR4 (TRAIL-R1) or DR5 (TRAIL-R2). In the last decade, the Apo2L/TRAIL system of apoptosis has attracted significant interest as a potential drug-targeting pathway for human therapy, due to the ability of that cytokine to trigger apoptosis in various types of cancer cells while displaying low or no toxicity to normal cells. Recent results suggest that manipulating the Apo2L/TRAIL system may be also useful for the treatment of inflammatory disorders such as rheumatoid arthritis. For its possible therapeutic use, a number of receptor-specific Apo2L/TRAIL molecular variants and agonistic monoclonal antibodies have been developed, and some of them are in clinical trials. In addition, Apo2L/TRAIL-resistant tumors can be sensitized to Apo2L/TRAIL by selected novel or classical chemotherapeutic agents, opening new possibilities for combined therapies. We will briefly review the current status of Apo2L/TRAIL-based therapies for human disease, their promises and limitations.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Martinez-Lostao L,Marzo I,Anel A,Naval J

doi

10.1016/j.bcp.2011.12.036

subject

Has Abstract

pub_date

2012-06-01 00:00:00

pages

1475-83

issue

11

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(11)00952-X

journal_volume

83

pub_type

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