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


  •   Ghadier Matariek

  •   John Oluwafemi Teibo

  •   Kholoud Elsamman

  •   Titilade Kehinde Ayandeyi Teibo

  •   David Idowu Olatunji

  •   Amira Matareek

  •   Olabode Ebenezer Omotoso

  •   Ahmed Nasr


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.

Keywords: Anti-neoplastic agents, breast cancer, resistance, selective estrogen receptor modulator, tamoxifen


World Health Organization. World Health Organization Model List of Essential Medicines. [Internet] 2019 Available from: https://apps.who.int/iris/bitstream/handle/10665/325771/WHO-MVP-EMP-IAU-2019.06-eng.pdf.

Schuurman TN, Witteveen PO, Van der Wall E, Passier JLM, Huitema ADR, Amant F, et al. Tamoxifen and pregnancy: an absolute contraindication? Breast Cancer Res Treat. 2019; 175(1): 17-25.

Klein DJ, Thorn CF, Desta Z, Flockhart DA, Altman RB, Klein TE. PharmGKB summary: tamoxifen pathway, pharmacokinetics. Pharmacogenetics and Genomics. 2013; 23(11): 643-647.

Novick AM, Scott AT, Neill-Epperson C, Schneck CD. Neuropsychiatric effects of tamoxifen: Challenges and opportunities. Front Neuroendocrinol. 2020; 59: 100-8.

Clifford RE, Bowden D, Blower E, Kirwan CC, Vimalachandran D. Does tamoxifen have a therapeutic role outside of breast cancer? A systematic review of the evidence. Surg Oncol. 2020; 33: 100-107.

Jordan VC. Tamoxifen: a personal retrospective. Lancet Oncol. 2000; 1(1): 43-49.

Jordan VC. The development of tamoxifen for breast cancer therapy: a tribute to the late Arthur L. Walpole. Breast Cancer Res Treat. 1988; 11(3): 197-209.

Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998; 90(18): 1371-1388.

Traboulsi T, El Ezzy M, Gleason JL Mader S. Antiestrogens: structure-activity relationships and use in breast cancer treatment. J Mol Endocrinol. 2017; 58(1): 15-31.

Shiina I, Suzuki M, Yokoyama K. Short-step synthesis of tamoxifen and its derivatives via the three-component coupling reaction and migration of the double bond. Tetrahedron Letters. 2004; 45(5): 965-967.

Matsumoto K, Shindo M. Palladium-Catalyzed Fluoride-Free Cross-Coupling of Intramolecularly Activated Alkenylsilanes and Alkenylgermanes: Synthesis of Tamoxifen as a Synthetic Application. Advanced Synthesis & Catalysis. 2012; 354(4): 642-650.

Fentiman IS, Fourquet A, Hortobagyi GN. Male breast cancer. Lancet. 2006; 367(9510): 595-604.

Abe O, Abe R, Enomoto K, Kikuchi K, Koyama H, Masuda H, et al. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005; 2005: 1687-1717.

Goss PE, Reid C, Pintilie M, Lim R, Miller N. Male breast carcinoma: a review of 229 patients who presented to the Princess Margaret Hospital during 40 years: 1955-1996. Cancer. 1999; 85(3): 629-639.

Steinitz R, Katz L, Ben-Hur M. Male breast cancer in Israel: selected epidemiological aspects. Isr J Med Sci. 1981; 17(9-10): 816-821.

Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013; 381(9869): 805-816.

Perez EA, Gandara DR, Edelman MJ, O'Donnell R, Lauder IJ, DeGregorio M. Phase I Trial of High-Dose Tamoxifen in Combination with Cisplatin in Patients with Lung Cancer and Other Advanced Malignancies. Cancer Investigation. 2003; 21(1): 1-6.

Chen YM, Perng RP, Whang-Peng J, Wu HW, Lin WC, Tsai CM. Phase II study with gemcitabine, ifosfamide and cisplatin in advanced non-small cell lung cancer. Lung Cancer. 2000; 30(3): 199-202.

Tomao S, Romiti A, Massidda B, Ionta MT, Farris A, Zullo A, et al. A phase II study of gemcitabine and tamoxifen in advanced pancreatic cancer. Anticancer Res. 2002; 22(4): 2361-2364.

Eckel F, Lersch C, Lippl F, Assmann G Schulte-Frohlinde E. Phase II trial of cyclophosphamide, leucovorin, 5-fluorouracil 24-hour infusion and tamoxifen in pancreatic cancer. J Exp Clin Cancer Res. 2000; 19(3): 295-300.

Lin CC, Hsu CH, Chen J, Tsai TC, Cheng AL, Pu YS. A pilot study of AFL-T (doxorubicin, 5-fluorouracil, leucovorin, and tamoxifen) combination chemotherapy for hormone-refractory prostate cancer. Anticancer Res. 2001; 21(2b): 1385-1390.

Zhang W, Anker L, Law RE, Hinton DR, Gopalakrishna R, Pu Q, et al. Enhancement of radiosensitivity in human malignant glioma cells by hypericin in vitro. Clin Cancer Res. 1996; 2(5): 843-846.

Pan DY, Qiao JG, Chen JW, Huo YC, Zhou YK, Shi HA. Tamoxifen combined with octreotide or regular chemotherapeutic agents in treatment of primary liver cancer: a randomized controlled trial. Hepatobiliary Pancreat Dis Int. 2003; 2(2): 211-215.

van Bommel EF, Hendriksz TR, Huiskes AW, Zeegers AG. Brief Communication: Tamoxifen Therapy for Nonmalignant Retroperitoneal Fibrosis. Annals of Internal Medicine. 2006; 144(2): 101-106.

Akram S, Pardi DS, Schaffner JA, Smyrk TC. Sclerosing mesenteritis: clinical features, treatment, and outcome in ninety-two patients. Clin Gastroenterol Hepatol. 2007; 5(5): 589-596.

Turken S, Siris E, Seldin D, Flaster E, Hyman G, Lindsay R. Effects of tamoxifen on spinal bone density in women with breast cancer. J Natl Cancer Inst. 1989; 81(14): 1086-1088.

McDonald CC, Alexander FE, Whyte BW, Forrest AP, Stewart HJ. Cardiac and vascular morbidity in women receiving adjuvant tamoxifen for breast cancer in a randomised trial. The Scottish Cancer Trials Breast Group. Bmj. 1995; 311(7011): 977-980.

Dabelic N, Jukic T, Labar Z, Novosel SA, Matesa N, Kusic Z. Riedel's thyroiditis treated with tamoxifen. Croat Med J. 2003; 44(2): 239-241.

Dic A, Carrabba G, Lanfranchi G, Menghetti C, Rampini P, Caroli M. Continuous tamoxifen and dose-dense temozolomide in recurrent glioblastoma. Anticancer Res. 2013; 33(8): 3383-3389.

Tang P, Roldan G, Brasher PM, Fulton D, Roa W, Murtha A, et al. A phase II study of carboplatin and chronic high-dose tamoxifen in patients with recurrent malignant glioma. J Neurooncol. 2006; 78(3): 311-316.

Weinländer G, Kornek G, Raderer M, Hejna M, Tetzner C, Scheithauer W. Treatment of advanced colorectal cancer with doxorubicin combined with two potential multidrug-resistance-reversing agents: high-dose oral tamoxifen and dexverapamil. J Cancer Res Clin Oncol. 1997; 123(8): 452-455.

Rusthoven JJ, Quirt IC, Iscoe NA, McCulloch PB, James KW, Lohmann RC, et al. Randomized, double-blind, placebo-controlled trial comparing the response rates of carmustine, dacarbazine, and cisplatin with and without tamoxifen in patients with metastatic melanoma. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1996; 14(7): 2083-2090.

Hu R, Hilakivi-Clarke L, Clarke R. Molecular mechanisms of tamoxifen-associated endometrial cancer (Review). Oncol Lett. 2015; 9(4): 1495-1501.

Musa MA, Khan MO, Cooperwood JS. Medicinal chemistry and emerging strategies applied to the development of selective estrogen receptor modulators (SERMs). Curr Med Chem. 2007; 14(11): 1249-1261.

Radin DP, Patel P. Delineating the molecular mechanisms of tamoxifen's oncolytic actions in estrogen receptor-negative cancers. Eur J Pharmacol. 2016; 781: 173-1780.

Scott SA, Selvy PE, Buck JR, Cho HP, Criswell TL, Thomas AL, et al. Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness. Nat Chem Biol. 2009; 5(2): 108-117.

Stancu C, Sima A. Statins: mechanism of action and effects. J Cell Mol Med. 2001; 5(4): 378-387.

Kitahara CM, Berrington de González A, Freedman ND, Huxley R, Mok Y, Jee SH, et al. Total cholesterol and cancer risk in a large prospective study in Korea. J Clin Oncol. 2011; 29(12): 1592-1598.

Nielsen SF, Nordestgaard BG, Bojesen SE. Statin Use and Reduced Cancer-Related Mortality. New England Journal of Medicine. 2012; 367(19): 1792-1802.

Ahern TP, Pedersen L, Tarp M, Cronin-Fenton DP, Garne JP, Silliman RA, et al. Statin prescriptions and breast cancer recurrence risk: a Danish nationwide prospective cohort study. J Natl Cancer Inst. 2011; 103(19): 1461-1468.

Ibrahim AB, Zaki HF, Ibrahim WW, Omran MM, Shouman SA. Evaluation of tamoxifen and simvastatin as the combination therapy for the treatment of hormonal dependent breast cancer cells. Toxicol Rep. 2019; 6: 1114-1126.

Gelber RD, Cole BF, Goldhirsch A, Rose C, Fisher B, Osborne CK, et al. Adjuvant chemotherapy plus tamoxifen compared with tamoxifen alone for postmenopausal breast cancer: meta-analysis of quality-adjusted survival. Lancet. 1996; 347(9008): 1066-1071.

Albain KS, Barlow WE, Ravdin PM, Farrar WB, Burton GV, Ketchel SJ, et al. Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009; 374(9707): 2055-2063.

Huh WJ, Khurana SS, Geahlen JH, Kohli K, Waller RA, Mills JC. Tamoxifen induces rapid, reversible atrophy, and metaplasia in mouse stomach. Gastroenterology. 2012; 142(1): 21-24.e7.

Kulkarni U, Nayak V, Prabhu MM, Rao R. Tamoxifen-induced vasculitis. J Oncol Pharm Pract. 2020; 26(3): 735-737.

Clarke MA, Long BJ, Del Mar Morillo A, Arbyn M, Bakkum-Gamez JN, Wentzensen N. Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women: A Systematic Review and Meta-analysis. JAMA Internal Medicine. 2018; 178(9): 1210-1222.

Tetikkurt S, Çelik E, Taş H, Cay T, Işik S, Usta AT. Coexistence of adenomyosis, adenocarcinoma, endometrial and myometrial lesions in resected uterine specimens. Mol Clin Oncol. 2018; 9(2): 231-237.

Choi SH, Kim KE, Park Y, Ju YW, Jung JG, Lee ES, et al. Effects of tamoxifen and aromatase inhibitors on the risk of acute coronary syndrome in elderly breast cancer patients: An analysis of nationwide data. Breast. 2020; 54: 25-30.

Etori S, Nakano R, Kamada H, Hosokawa K, Takeda S, Fukuhara M, et al. Tamoxifen-induced Lung Injury. Intern Med. 2017; 56(21): 2903-2906.

Yao J, Deng K, Huang J, Zeng R, Zuo J. Progress in the Understanding of the Mechanism of Tamoxifen Resistance in Breast Cancer. Front Pharmacol. 2020; 11(5): 592-9.

Karlsson E, Veenstra C, Gårsjö J, Nordenskjöld B, Fornander T, Stål O. PTPN2 deficiency along with activation of nuclear Akt predict endocrine resistance in breast cancer. J Cancer Res Clin Oncol. 2019; 145(3): 599-607.

Zhu Y, Liu Y, Zhang C, Chu J, Wu Y, Li Y, et al. Tamoxifen-resistant breast cancer cells are resistant to DNA-damaging chemotherapy because of upregulated BARD1 and BRCA1. Nat Commun. 2018; 9(1): 1595.

Peng WX, Huang JG, Yang L, Gong AH, Mo YY. Linc-RoR promotes MAPK/ERK signaling and confers estrogen-independent growth of breast cancer. Mol Cancer. 2017; 16(1): 161.

Mansouri S, Feizi N, Mahdi A, Majidzadeh AK Farahmand L. A Review on The Role of VEGF in Tamoxifen Resistance. Anticancer Agents Med Chem. 2018; 18(14): 2006-2009.

Gao A, Sun T, Ma G, Cao J, Hu Q, Chen L, et al. LEM4 confers tamoxifen resistance to breast cancer cells by activating cyclin D-CDK4/6-Rb and ERα pathway. Nat Commun. 2018; 9(1).

Yin L, Zhang XT, Bian XW, Guo YM, Wang ZY. Disruption of the ER-α36-EGFR/HER2 positive regulatory loops restores tamoxifen sensitivity in tamoxifen resistance breast cancer cells. PLoS One. 2014; 9(9): 10-17.

Grant MC, Geoghegan L, Arbyn M, Mohammed Z, McGuinness L, Clarke EL, et al. The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries. PLoS One. 2020; 15(6): 23-47.

Ito T, Kamijo S, Izumi H, Kohno K, Amano J, Ito K. Alteration of Y-box binding protein-1 expression modifies the response to endocrine therapy in estrogen receptor-positive breast cancer. Breast Cancer Res Treat. 2012; 133(1): 145-59.

Vaziri-Gohar A, Zheng Y, Houston KD. IGF-1 Receptor Modulates FoxO1-Mediated Tamoxifen Response in Breast Cancer Cells. Mol Cancer Res. 2017; 15(4): 489-497.

Zhang Y, Wester L, He J, Geiger T, Moerkens M, Siddappa R, et al. IGF1R signaling drives antiestrogen resistance through PAK2/PIX activation in luminal breast cancer. Oncogene. 2018; 37(14): 1869-1884.

Xue Y, Lian W, Zhi J, Yang W, Li Q, Guo X, et al. HDAC5-mediated deacetylation and nuclear localisation of SOX9 is critical for tamoxifen resistance in breast cancer. British Journal of Cancer. 2019; 121(12): 1039-1049.

Thomas S, Thurn KT, Raha P, Chen S, Munster PN. Efficacy of histone deacetylase and estrogen receptor inhibition in breast cancer cells due to concerted down regulation of Akt. PLoS One. 2013; 8(7): 68-97.

Maczis MA, Maceyka M, Waters MR, Newton J, Singh M, Rigsby MF, et al. Sphingosine kinase 1 activation by estrogen receptor α36 contributes to tamoxifen resistance in breast cancer. J Lipid Res. 2018; 59(12): 2297-2307.

Shen Y, Zhong J, Liu J, Liu K, Zhao J, Xu T, et al. Protein arginine N-methyltransferase 2 reverses tamoxifen resistance in breast cancer cells through suppression of ER-α36. Oncol Rep. 2018; 39(6): 2604-2612.

Yu D, Shi L, Bu Y, Li W. Cell Division Cycle Associated 8 Is a Key Regulator of Tamoxifen Resistance in Breast Cancer. J Breast Cancer. 2019; 22(2): 237-247.

Ye L, Lin C, Wang X, Li Q, Li Y, Wang M, et al. Epigenetic silencing of SALL2 confers tamoxifen resistance in breast cancer. EMBO Mol Med. 2019; 11(12): e10638.

Shimoda M, Hori A, Wands JR, Tsunashima R, Naoi Y, Miyake T, et al. Endocrine sensitivity of estrogen receptor-positive breast cancer is negatively correlated with aspartate-β-hydroxylase expression. Cancer Science. 2017; 108(12): 2454-2461.

Gwak JM, Kim M, Kim HJ, Jang MH, Park SY. Expression of embryonal stem cell transcription factors in breast cancer: Oct4 as an indicator for poor clinical outcome and tamoxifen resistance. Oncotarget. 2017; 8(22): 36305-36318.

Cheng R, Liu YJ, Cui JW, Yang M, Liu XL, Li P, et al. Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen resistance in estrogen receptor-positive breast cancer cells. Oncotarget. 2017; 8(18): 30252-30264.

Viedma-Rodríguez R, Baiza-Gutman L, Salamanca-Gómez F, Diaz-Zaragoza M, Martínez-Hernández G, Ruiz Esparza-Garrido R, et al. Mechanisms associated with resistance to tamoxifen in estrogen receptor-positive breast cancer (review). Oncol Rep. 2014; 32(1): 3-15.

Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. N Engl J Med. 2016; 375(18): 1738-1748.

Ferraiuolo RM, Tubman J, Sinha I, Hamm C, Porter LA. The cyclin-like protein, SPY1, regulates the ERα and ERK1/2 pathways promoting tamoxifen resistance. Oncotarget. 2017; 8(14): 23337-23352.

Zhang Y, Lv C, Dong Y, Yang Q. Aspirin-targeted PD-L1 in lung cancer growth inhibition. Thorac Cancer. 2020; 11(6): 1587-1593.

Jiang MJ, Chen YY, Dai JJ, Gu DN, Mei Z, Liu FR, et al. Dying tumor cell-derived exosomal miR-194-5p potentiates survival and repopulation of tumor repopulating cells upon radiotherapy in pancreatic cancer. Molecular Cancer. 2020; 19(1): 68-75.

Maqbool SN, Lim SC, Park KC, Hanif R, Richardson DR, Jansson PJ, et al. Overcoming tamoxifen resistance in oestrogen receptor-positive breast cancer using the novel thiosemicarbazone anti-cancer agent, DpC. Br J Pharmacol. 2020; 177(10): 2365-2380.

Mishra RR, Belder N, Ansari SA, Kayhan M, Bal H, Raza U, et al. Reactivation of cAMP Pathway by PDE4D Inhibition Represents a Novel Druggable Axis for Overcoming Tamoxifen Resistance in ER-positive Breast Cancer. Clin Cancer Res. 2018; 24(8): 1987-2001.

Li L, Hu M, Wang T, Chen H, Xu L. Repositioning Aspirin to Treat Lung and Breast Cancers and Overcome Acquired Resistance to Targeted Therapy. Front Oncol. 2019; 9(2): 1503-8.

Block M, Gründker C, Fister S, Kubin J, Wilkens L, Mueller MD, et al. Inhibition of the AKT/mTOR and erbB pathways by gefitinib, perifosine and analogs of gonadotropin-releasing hormone I and II to overcome tamoxifen resistance in breast cancer cells. Int J Oncol. 2012; 41(5): 1845-1854.

Giordano C, Catalano S, Panza S, Vizza D, Barone I, Bonofiglio D, et al. Farnesoid X receptor inhibits tamoxifen-resistant MCF-7 breast cancer cell growth through downregulation of HER2 expression. Oncogene. 2011; 30(39): 4129-4140.

Jeong Y, Bae SY, You D, Jung SP, Choi HJ, Kim I, et al. EGFR is a Therapeutic Target in Hormone Receptor-Positive Breast Cancer. Cell Physiol Biochem. 2019; 53(5): 805-819.

Kim S, Lee J, Oh SJ, Nam SJ, Lee JE. Differential effect of EGFR inhibitors on tamoxifen-resistant breast cancer cells. Oncol Rep. 2015; 34(3): 1613-1619.

Woo SH, Seo SK, Park Y, Kim EK, Seong MK, Kim HA, et al. Dichloroacetate potentiates tamoxifen-induced cell death in breast cancer cells via downregulation of the epidermal growth factor receptor. Oncotarget. 2016; 7(37): 59809-59819.

Huang S, Chen Y, Liang ZM, Li NN, Liu Y, Zhu Y, et al. Targeting Pin1 by All-Trans Retinoic Acid (ATRA) Overcomes Tamoxifen Resistance in Breast Cancer via Multifactorial Mechanisms. Front Cell Dev Biol. 2019; 7(2): 322-9.

Das CK, Parekh A, Parida PK, Bhutia SK, Mandal M. Lactate dehydrogenase A regulates autophagy and tamoxifen resistance in breast cancer. Biochim Biophys Acta Mol Cell Res. 2019; 1866(6): 1004-1018.

Tavassoli M, Soltaninia J, Rudnicka J, Mashanyare D, Johnson N, Gäken J. Tamoxifen inhibits the growth of head and neck cancer cells and sensitizes these cells to cisplatin induced-apoptosis: role of TGF-β1. Carcinogenesis. 2002; 23(10): 1569-1575.

Nakata B, Albright KD, Barton RM, Howell SB, Los G. Synergistic interaction between cisplatin and tamoxifen delays the emergence of cisplatin resistance in head and neck cancer cell lines. Cancer Chemotherapy and Pharmacology. 1995; 35(6): 511-518.

Chu ST, Huang CC, Huang CJ, Cheng JS, Chai KL, Cheng HH, et al. Tamoxifen-Induced [Ca2+]i Rises and Ca2+-Independent Cell Death in Human Oral Cancer Cells. Journal of Receptors and Signal Transduction. 2007; 27(5-6): 353-367.

Ferrandina G, Almadori G, Maggiano N, Lanza P, Ferlini C, Cattani P, et al. Growth-inhibitory effect of tamoxifen and quercetin and presence of type II estrogen binding sites in human laryngeal cancer cell lines and primary laryngeal tumors. Int J Cancer. 1998; 77(5): 747-754.

Morad SA, Ryan TE, Neufer PD, Zeczycki TN, Davis TS, MacDougall MR, et al. Ceramide-tamoxifen regimen targets bioenergetic elements in acute myelogenous leukemia. J Lipid Res. 2016; 57(7): 1231-1242.

Morad SAF, Davis TS, MacDougall MR, Tan SF, Feith DJ, Desai DH, et al. Role of P-glycoprotein inhibitors in ceramide-based therapeutics for treatment of cancer. Biochem Pharmacol. 2017; 130(7): 21-33.

Torres-López L, Maycotte P, Liñán-Rico A, Liñán-Rico L, Donis-Maturano L, Delgado-Enciso I, et al. Tamoxifen induces toxicity, causes autophagy, and partially reverses dexamethasone resistance in Jurkat T cells. J Leukoc Biol. 2019; 105(5): 983-998.

Wang X, Chen Q, Huang X, Zou F, Fu Z, Chen Y, et al. Effects of 17β-estradiol and tamoxifen on gastric cancer cell proliferation and apoptosis and ER-α36 expression. Oncology Letters. 2017; 13(1): 57-62.

Mao Z, Zhou J, Luan J, Sheng W, Shen X, Dong X. Tamoxifen reduces P-gp-mediated multidrug resistance via inhibiting the PI3K/Akt signaling pathway in ER-negative human gastric cancer cells. Biomed Pharmacother. 2014; 68(2): 179-183.

Hosoya Y, Kitoh Y, Kobayashi E, Okabe R, Fujimura A, Kanazawa K. Combination effects of tamoxifen plus 5-fluorouracil on gastric cancer cell lines in vitro. Cancer Lett. 1999; 140(1): 139-143.

Takeuchi H, Mmeje CO, Jinesh GG, Taoka R, Kamat AM. Sequential gemcitabine and tamoxifen treatment enhances apoptosis and blocks transformation in bladder cancer cells. Oncology Reports. 2015; 34(5): 2738-2744.

Pu YS, Hsieh TS, Cheng AL, Tseng NF, Su IJ, Hsieh CY, et al. Combined cytotoxic effects of tamoxifen and chemotherapeutic agents on bladder cancer cells: a potential use in intravesical chemotherapy. British Journal of Urology. 1996; 77(1): 76-85.


Download data is not yet available.


How to Cite
Matariek, G. ., Teibo, J. O., Elsamman, K., Teibo, T. K. A., Olatunji, D. I. ., Matareek, A. ., Omotoso, O. E. ., & Nasr, A. . (2022). Tamoxifen: The Past, Present, and Future of a Previous Orphan Drug. European Journal of Medical and Health Sciences, 4(3), 1–10. https://doi.org/10.24018/ejmed.2022.4.3.1124