Toll like receptor signaling pathway as a potential therapeutic target in colorectal cancer

Abstract

Toll like receptor (TLR) signaling is involved in activating innate and adaptive immune responses and plays a critical role in inflammation-induced diseases such as colorectal cancer (CRC). Dysregulation of this signaling pathway can result in disturbance of epithelial layer hemostasis, chronic inflammatory, excessive repair responses, and development of CRC. There is now substantial evidence for the benefit of targeting of this pathway in cancer treatment, and several agents have been approved, such as BCG (Bacillus Calmette Guérin), MPL (monophosphoryl lipid A) and imiquimod. This review summarizes the current knowledge about the different functions of TLRs on tumor cells and their application in cancer therapy with particular emphasis on recent preclinical and clinical research in treatment of CRC.

Reactive oxygen species in colorectal cancer: The therapeutic impact and its potential roles in tumor progression via perturbation of cellular and physiological dysregulated pathways

“…CRC is classified as the third most common malignancy in the world (Moradi‐Marjaneh et al, ; Moradi‐Marjaneh, Khazaei, et al, ). One of the contributory causes of CRC is the effect of ROS on signaling pathways and transcription factors (H. Liu et al, ).…”

Prognostic role of Toll-like receptors in cancer: a meta-analysis

“…TLRs that are activated by their individual ligands could recruit MyD88 and subsequently activate the downstream targets, including nuclear factor of kappa B, mitogen-associated protein kinase, and interferon regulatory factors 2. Furthermore, recently, numerous studies have demonstrated that TLRs could be involved in antitumor or protumor responses 45,46. For example, TLR4-deficient mice have showed enhanced tumorigenesis in inducible model of lung cancer, skin cancer, and BC.…”

Hsp70 inhibitors: Implications for the treatment of colorectal cancer

“…The incidence and mortality rates of CRC are estimated to reach 2.2 million new cases and 1.1 million deaths in 2030 . Although multiple combination chemotherapeutic regimens such as FOLFIRI, XELOX/CAPOX, and FOLFOX are widely used clinical treatments for CRC, it is still remained as a main cancer‐related death cause due to recurrent or metastatic disease, supporting the need for novel therapeutic approaches …”