title: New frontiers in the treatment of colorectal cancer: Autophagy and the unfolded protein response as promising targets.
abstract: Colorectal cancer (CRC), despite numerous therapeutic and screening attempts, still remains a major life-threatening malignancy. CRC etiology entails both genetic and environmental factors. Macroautophagy/autophagy and the unfolded protein response (UPR) are fundamental mechanisms involved in the regulation of cellular responses to environmental and genetic stresses. Both pathways are interconnected and regulate cellular responses to apoptotic stimuli. In this review, we address the epidemiology and risk factors of CRC, including genetic mutations leading to the occurrence of the disease. Next, we discuss mutations of genes related to autophagy and the UPR in CRC. Then, we discuss how autophagy and the UPR are involved in the regulation of CRC and how they associate with obesity and inflammatory responses in CRC. Finally, we provide perspectives for the modulation of autophagy and the UPR as new therapeutic options for CRC treatment.
authors.affiliation: a Colorectal Research Center and Department of Biochemistry , School of Medicine, Shiraz University of Medical Sciences , Shiraz , Iran.
authors.forename: Pooneh
authors.initials: P
authors.lastname: Mokarram
authors.affiliation: b Department of Human Anatomy and Cell Science , Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba , Winnipeg , MB , Canada.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Albokashy
authors.affiliation: c Zabol University of Medical Sciences , Zabol , Iran.|d University of Toronto Alumni , Toronto , ON , Canada.
authors.forename: Maryam
authors.initials: M
authors.lastname: Zarghooni
authors.affiliation: e Department of Molecular Medicine , Institute of Medical Biotechnology, National Institute for Genetic Engineering and Biotechnology , Tehran , Iran.
authors.forename: Mohammad Amin
authors.initials: MA
authors.lastname: Moosavi
authors.affiliation: c Zabol University of Medical Sciences , Zabol , Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Sepehri
authors.affiliation: b Department of Human Anatomy and Cell Science , Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba , Winnipeg , MB , Canada.
authors.forename: Qi Min
authors.initials: QM
authors.lastname: Chen
authors.affiliation: f Institute of Nonferrous Metals , Gliwice , Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hudecki
authors.affiliation: c Zabol University of Medical Sciences , Zabol , Iran.
authors.forename: Aliyeh
authors.initials: A
authors.lastname: Sargazi
authors.affiliation: b Department of Human Anatomy and Cell Science , Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba , Winnipeg , MB , Canada.
authors.forename: Javad
authors.initials: J
authors.lastname: Alizadeh
authors.affiliation: b Department of Human Anatomy and Cell Science , Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba , Winnipeg , MB , Canada.
authors.forename: Adel Rezaei
authors.initials: AR
authors.lastname: Moghadam
authors.affiliation: g Department of Clinical Biochemistry , School of Medicine, Zahedan University of Medical Sciences , Zahedan , Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hashemi
authors.affiliation: h Department of Immunology , Rady Faculty of Health Sciences, College of Medicine, University of Manitoba , Winnipeg , MB , Canada.
authors.forename: Hesam
authors.initials: H
authors.lastname: Movassagh
authors.affiliation: b Department of Human Anatomy and Cell Science , Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba , Winnipeg , MB , Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klonisch
authors.affiliation: i Department of Clinical Biochemistry , School of Medicine, Shiraz Medical University , Shiraz , Iran.
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Owji
authors.affiliation: j Małopolska Centre of Biotechnology , Jagiellonian University , Krakow , Poland ; LinkoCare Life Sciences AB , Sweden.
authors.forename: Marek J
authors.initials: MJ
authors.lastname: Łos
authors.affiliation: b Department of Human Anatomy and Cell Science , Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba , Winnipeg , MB , Canada.|k Health Policy Research Center , Shiraz University of Medical Sciences , Shiraz , Iran.
authors.forename: Saeid
authors.initials: S
authors.lastname: Ghavami
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001343:Autophagy / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000628:therapy; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000628:therapy; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D006801:Humans; D056811:Unfolded Protein Response / Q000235:genetics*
keywords: Beclin 1; ER-stress; GRP78; autophagy; cancer therapy; colorectal cancer; unfolded protein response