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Tamoxifen: The Past, Present, and Future of a Previous Orphan Drug

Author

Listed:
  • Ghadier Matariek
  • John Oluwafemi Teibo
  • Kholoud Elsamman
  • Titilade Kehinde Ayandeyi Teibo
  • David Idowu Olatunji
  • Amira Matareek
  • Olabode Ebenezer Omotoso
  • Ahmed Nasr

Abstract

Tamoxifen, a non-steroidal selective estrogen receptor modulator is a widely used drug for the prevention and breast cancer treatment. It binds to the hormone-receptors to prevent the binding of the cancer cells in the breast to the hormones they need for growth. It undergoes metabolic activation which converts it to an active metabolite (endoxifen and afimoxifene) by the action of cytochromeP450 isoforms CYP2C9, CYP2D6, CYP3A4. Notable among its side effects include hot flashes, weight loss, endometrial and uterine cancer, irregular periods, stroke, abnormal fetal development in pregnant women and others discussed in our review. Other than breast cancer, medicinal potential of tamoxifen has been probed in several therapeutic targets. The outcome has shown great promise in managing osteoporosis, infertility, advanced gliomas, lung and liver cancer, among many others. The major drawbacks on the use of tamoxifen have been centered on its resistance and associated side effects. Some of the notable future direction of tamoxifen is centered on overcoming its resistance as well as repurposing of tamoxifen in wider cancer settings. Targeting LEM4 as a biomarker for predicting tamoxifen resistance in ER-positive breast cancer could be a viable research area in the future to overcome tamoxifen resistance.

Suggested Citation

  • Ghadier Matariek & John Oluwafemi Teibo & Kholoud Elsamman & Titilade Kehinde Ayandeyi Teibo & David Idowu Olatunji & Amira Matareek & Olabode Ebenezer Omotoso & Ahmed Nasr, 2022. "Tamoxifen: The Past, Present, and Future of a Previous Orphan Drug," European Journal of Medical and Health Sciences, European Open Science, vol. 4(3), pages 1-10, May.
    • Handle: RePEc:epw:ejmed0:v:4:y:2022:i:3:id:41124
    DOI: 10.24018/ejmed.2022.4.3.1124
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    1. Ang Gao & Tonghua Sun & Gui Ma & Jiangran Cao & Qingxia Hu & Ling Chen & Yanxin Wang & Qianying Wang & Jiafu Sun & Rui Wu & Qiao Wu & Jiaxi Zhou & Lin Liu & Junjie Hu & Jin-Tang Dong & Zhengmao Zhu, 2018. "LEM4 confers tamoxifen resistance to breast cancer cells by activating cyclin D-CDK4/6-Rb and ERĪ± pathway," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    2. Yinghua Zhu & Yujie Liu & Chao Zhang & Junjun Chu & Yanqing Wu & Yudong Li & Jieqiong Liu & Qian Li & Shunying Li & Qianfeng Shi & Liang Jin & Jianli Zhao & Dong Yin & Sol Efroni & Fengxi Su & Herui Y, 2018. "Tamoxifen-resistant breast cancer cells are resistant to DNA-damaging chemotherapy because of upregulated BARD1 and BRCA1," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
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