Targeting the death receptor signaling pathway as a potential therapeutic target in the treatment of colorectal cancer.

Reyhaneh Moradi Marjaneh, Seyed Mahdi Hassanian, Niloofar Ghobadi, Gordon A Ferns, Afshin Karimi, Mir Hadi Jazayeri, Mohammadreza Nasiri, Amir Avan, Majid Khazaei

Journal: Journal of cellular physiology 2019;233(10):6538-6549

PMID: 29741789

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Abstract

Despite advances in the diagnosis and treatment of colorectal cancer (CRC), it remains a major cause of cancer related death globally. There are currently no chemotherapeutic agents that have been found to eradicate the disease without adverse effects. A defect in the death receptor signaling pathway is a feature of CRC. The ligand of these receptors belongs to the tumor necrosis factor family, and that are particularly expressed by cells of the immune system, and that induce apoptosis in a caspase dependent manner. The fact that malignant cells are particularly sensitive to these ligands, compared to normal cells, has led to work on the assessment of compounds that activate this pathway in the treatment of CRC. Phase I trials have shown that these death receptor agonists are safe. Phase II and III trials are currently investigating the efficacy of these therapeutic agents in the treatment of CRC. In this review, we describe the biochemical death receptor signaling pathway and its relationship to CRC. We also summarize the current clinical studies that are targeting this signaling pathway in CRC treatment.

Address: Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.; Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.; Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.; Microanatomy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.; Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.; Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex, UK.; Quality Department of Nutricia, Mashhad Mild Powder Industrial, Mashhad, Iran.; Immunology Research Center and Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.; Recombinant Proteins Research Group, The Research Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.; Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.; Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.; Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.; Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

DOI: 10.1002/jcp.26640

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https://doi.org/10.1002/jcp.26640

MeSH Terms: Apoptosis, Cell Proliferation, Clinical Trials as Topic, Colorectal Neoplasms, Humans, Receptors, Death Domain, Signal Transduction, Tumor Necrosis Factor-alpha