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

Fundam Clin Pharmacol. 2023 Dec;37(6):1092-1108. doi: 10.1111/fcp.12936. Epub 2023 Jul 4.

Abstract

Background: 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.

Objective: This review explored the literature on the connections between hormonal therapies and autophagy. We investigated how autophagy could develop drug resistance in BC cells.

Methods: Scopus, Science Direct, PubMed, and Google Scholar were used to search articles for this study.

Results: 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.

Conclusion: Therefore, by overcoming endocrine resistance in estrogen receptor-positive breast tumors, autophagy inhibition may improve the therapeutic efficacy of TAM.

Keywords: anticancer properties; autophagy; breast cancer; tamoxifen.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Hormonal / pharmacology
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Autophagy
  • Breast Neoplasms* / metabolism
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Receptors, Estrogen / therapeutic use
  • Tamoxifen* / pharmacology
  • Tamoxifen* / therapeutic use

Substances

  • Tamoxifen
  • Receptors, Estrogen
  • Antineoplastic Agents, Hormonal