Targeting autophagy with tamoxifen in breast cancer: From molecular mechanisms to targeted therapy

Tamoxifen (TAM) is often recommended as a first-line treatment for estrogen receptor-positive breast cancer (BC). However, TAM resistance continues to be a medical challenge for BC with hormone receptor positivity. The function of macro-autophagy and autophagy has recently been identified to be alte...

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Published in:Fundamental & clinical pharmacology 2023-12, Vol.37 (6), p.1092-1108
Main Authors: Zamanian, Mohammad Yasin, Golmohammadi, Maryam, Nili-Ahmadabadi, Amir, Alameri, Ameer A, Al-Hassan, Mohammed, Alshahrani, Shadia Hamoud, Hasan, Mohammed Sami, Ramírez-Coronel, Andrés Alexis, Qasim, Qutaiba A, Heidari, Mahsa, Verma, Amita
Format: Article
Language:English
Subjects:
Autophagy
Breast cancer
Cytotoxicity
Drug resistance
Estrogen receptors
Estrogens
Homeostasis
Kinases
Literature reviews
Molecular modelling
Pharmacology
Receptors
Search engines
Tamoxifen
Tumor cells
Tumors
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Summary:Tamoxifen (TAM) is often recommended as a first-line treatment for estrogen receptor-positive breast cancer (BC). However, TAM resistance continues to be a medical challenge for BC with hormone receptor positivity. The function of macro-autophagy and autophagy has recently been identified to be altered in BC, which suggests a potential mechanism for TAM resistance. Autophagy is a cellular stress-induced response to preserve cellular homeostasis. Also, therapy-induced autophagy, which is typically cytoprotective and activated in tumor cells, could sometimes be non-protective, cytostatic, or cytotoxic depending on how it is regulated. This review explored the literature on the connections between hormonal therapies and autophagy. We investigated how autophagy could develop drug resistance in BC cells. Scopus, Science Direct, PubMed, and Google Scholar were used to search articles for this study. The results demonstrated that protein kinases such as pAMPK, BAX, and p-p70S6K could be a sign of autophagy in developing TAM resistance. According to the study's findings, autophagy plays an important role in BC patients' TAM resistance. Therefore, by overcoming endocrine resistance in estrogen receptor-positive breast tumors, autophagy inhibition may improve the therapeutic efficacy of TAM.
ISSN:0767-3981
1472-8206
DOI:10.1111/fcp.12936