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Should a Toll-like receptor 4 (TLR-4) agonist or antagonist be designed to treat cancer? TLR-4: its expression and effects in the ten most common cancers

Authors Mai CW, Kang YB, Pichika MR

Received 1 July 2013

Accepted for publication 13 August 2013

Published 5 November 2013 Volume 2013:6 Pages 1573—1587

DOI https://doi.org/10.2147/OTT.S50838

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Chun Wai Mai, Yew Beng Kang, Mallikarjuna Rao Pichika

Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia

Abstract: Toll-like receptor 4 (TLR-4) is well known for its host innate immunity. Despite the fact that TLR-4 activation confers antitumor responses; emerging evidence suggests that TLR-4 is associated with tumor development and progression. It is now clear that overactivation of TLR-4, through various immune mediators, may cause immune response dysfunction, resulting in tumorigenesis. Different cancers could have different extents of TLR-4 involvement during tumorigenesis or tumor progression. In this review, we focus on infection- and inflammation-related TLR-4 activation in noncancer and cancer cells, as well as on the current evidence about the role of TLR-4 in ten of the most common cancers, viz, head and neck cancer, lung cancer, gastrointestinal cancer, liver cancer, pancreatic cancer, skin cancer, breast cancer, ovarian cancer, cervical cancer, and prostate cancer.

Keywords: drug design, cancer treatment, myeloid differentiation factor 2, MD-2, tumor progression, pathogen-associated molecular patterns, PAMPs

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