New Insight into Triple-Negative Breast Cancer Therapy: The Potential Roles of Endoplasmic Reticulum Stress and Autophagy Mechanisms

Author(s):

Milad Ashrafizadeh, Reza Mohammadinejad, Shima Tavakol, Zahra Ahmadi and Amirhossein Sahebkar*   Pages 679 - 691 ( 13 )

Abstract:

<P>Background: Breast cancer is accounted as the fifth leading cause of mortality among the other cancers. Notwithstanding, Triple Negative Breast Cancer (TNBC) is responsible for 15-20% of breast cancer mortality. Despite many investigations, it remains incurable in part due to insufficient understanding of its exact mechanisms. </P><P> Methods: A literature search was performed in PubMed, SCOPUS and Web of Science databases using the keywords autophagy, Endoplasmic Reticulum (ER) stress, apoptosis, TNBC and the combinations of these keywords. </P><P> Results: It was found that autophagy plays a dual role in cancer, so that it may decrease the viability of tumor cells or act as a cytoprotective mechanism. It then appears that using compounds having modulatory effects on autophagy is of importance in terms of induction of autophagic cell death and diminishing the proliferation and metastasis of tumor cells. Also, ER stress can be modulated in order to stimulate apoptotic and autophagic cell death in tumor cells. </P><P> Conclusion: Perturbation in the signaling pathways related to cell survival leads to the initiation and progression of cancer. Regarding the advancement in the cancer pathology, it seems that modulation of autophagy and ER stress are promising.</P>

Keywords:

Triple-negative breast cancer, endoplasmic reticulum stress, autophagy, apoptosis, cell death, cytoprotective mechanism.

Affiliation:

Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Department of Basic Science, Faculty of Veterinary Medicine, Islamic Azad Branch, University of Shushtar, Khuzestan, Halal Research Center of IRI, FDA, Tehran

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