RT Journal Article SR Electronic T1 Therapeutic Targeting of Toll-Like Receptors for Infectious and Inflammatory Diseases and Cancer JF Pharmacological Reviews JO Pharmacol Rev FD American Society for Pharmacology and Experimental Therapeutics SP 177 OP 197 DO 10.1124/pr.109.001073 VO 61 IS 2 A1 Luke A. J. O'Neill A1 Clare E. Bryant A1 Sarah L. Doyle YR 2009 UL http://pharmrev.aspetjournals.org/content/61/2/177.abstract AB Since first being described in the fruit fly Drosophila melanogaster, Toll-like receptors (TLRs) have proven to be of great interest to immunologists and investigators interested in the molecular basis to inflammation. They recognize pathogen-derived factors and also products of inflamed tissue, and trigger signaling pathways that lead to activation of transcription factors such as nuclear factor-κB and the interferon regulatory factors. These in turn lead to induction of immune and inflammatory genes, including such important cytokines as tumor necrosis factor-α and type I interferon. Much evidence points to a role for TLRs in immune and inflammatory diseases and increasingly in cancer. Examples include clear roles for TLR4 in sepsis, rheumatoid arthritis, ischemia/reperfusion injury, and allergy. TLR2 has been implicated in similar pathologic conditions and also in systemic lupus erythematosus (SLE) and tumor metastasis. TLR7 has also been shown to be important in SLE. TLR5 has been shown to be radioprotective. Recent advances in our understanding of signaling pathways activated by TLRs, structural insights into TLRs bound to their ligands and antagonists, and approaches to inhibit TLRs (including antibodies, peptides, and small molecules) are providing possiblemeans by which to interfere with TLRs clinically. Here we review these recent advances and speculate about whether manipulating TLRs is likely to be successful in fighting off different diseases.