Tamoxifen and Endometrial Cancer: A Janus-Headed Drug

Emons, Günter; Mustea, Alexander; Tempfer, Clemens

doi:10.3390/cancers12092535

Cited by 54 publications

(36 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tamoxifen belongs to the group of selective estrogen modulators (SERMs), which act as agonists or antagonists on the ER, depending on the tissue type, but several authors suggest that the activation-inhibition profile also depends on the receptor isoform and their ratio in a cell [ 30 , 35 ]. In the breast and pancreas tissues, tamoxifen is a well-known antagonist of the estrogen receptor α and β, but it is an agonist on the GPER1 [ 36 , 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is a well-described phenomenon that GPER1 signaling promotes tumor progression [ 85 , 86 ], helps cancer cells to obtain stem cell-like properties [ 87 ], and can mediate therapy resistance [ 88 , 89 ]. The presence of GPER1 poses a clinical problem as well, as patients with GPER1 expressing tumors have a worse survival rate, compared to patients with non-GPER1 expressing tumors, when receiving tamoxifen therapy [ 90 , 91 , 92 ], mostly because tamoxifen was described to be an agonist of GPER1 [ 36 , 37 , 38 ], inducing its previously mentioned tumor-promoting capability.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Investigation of the Antitumor Effects of Tamoxifen and Its Ferrocene-Linked Derivatives on Pancreatic and Breast Cancer Cell Lines

et al. 2022

View full text Add to dashboard Cite

Tamoxifen is a long-known anti-tumor drug, which is the gold standard therapy in estrogen receptor (ER) positive breast cancer patients. According to previous studies, the conjugation of the original tamoxifen molecule with different functional groups can significantly improve its antitumor effect. The purpose of this research was to uncover the molecular mechanisms behind the cytotoxicity of different ferrocene-linked tamoxifen derivates. Tamoxifen and its ferrocene-linked derivatives, T5 and T15 were tested in PANC1, MCF7, and MDA-MB-231 cells, where the incorporation of the ferrocene group improved the cytotoxicity on all cell lines. PANC1, MCF7, and MDA-MB-231 express ERα and GPER1 (G-protein coupled ER 1). However, ERβ is only expressed by MCF7 and MDA-MB-231 cells. Tamoxifen is a known agonist of GPER1, a receptor that can promote tumor progression. Analysis of the protein expression profile showed that while being cytotoxic, tamoxifen elevated the levels of different tumor growth-promoting factors (e.g., Bcl-XL, Survivin, EGFR, Cathepsins, chemokines). On the other hand, the ferrocene-linked derivates were able to lower these proteins. Further analysis showed that the ferrocene-linked derivatives significantly elevated the cellular oxidative stress compared to tamoxifen treatment. In conclusion, we were able to find two molecules possessing better cytotoxicity compared to their unmodified parent molecule while also being able to counter the negative effects of the presence of the GPER1 through the ER-independent mechanism of oxidative stress induction.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Investigation of the Antitumor Effects of Tamoxifen and Its Ferrocene-Linked Derivatives on Pancreatic and Breast Cancer Cell Lines

et al. 2022

View full text Add to dashboard Cite

show abstract

“…A study claimed that 70.7% of the patients with BC will be diagnosed with EC within 5 years ( 57 ). Tamoxifen increases the risk of developing EC by 2–7 fold, and aggressive EC types with poor prognosis have been observed among tamoxifen users ( 75 ). The long-term use of tamoxifen resulted in a 59% higher risk of EC-related death in women who had received it for 5 years or more than in women who had not ( 80 ).…”

Section: Mpcs Associated With Bc and Ecmentioning

confidence: 99%

Common Multiple Primary Cancers Associated With Breast and Gynecologic Cancers and Their Risk Factors, Pathogenesis, Treatment and Prognosis: A Review

Wang

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

The mammary gland is closely related to the female reproductive system in many aspects, affecting the whole gynecological system. Breast cancer (BC) is the most common malignancy in women and associated with considerable negative effects. Due to various factors including co-pathogenic genetic mutations, environment factors, lifestyle, behavioral factors, treatment regimens and in-creased survival of patients with BC, there is an increased probability of developing additional primary gynecologic cancers such as ovarian cancer (OC), endometrial cancer (EC), and cervical cancer (CC). More and more studies have been conducted in recent years. Multiple primary cancers (MPCs), also known as multiple primary malignancies, refers to two or more different primary cancers in the same patient occurring in the same or different organs or tissues. The pathogenesis of multiple primary cancers is complex and has a negative effect on the prognosis and survival of patients. This review discusses the common types of BC-associated MPCs, namely, BC associated with OC, BC associated with EC and BC associated with CC, as well as risk factors, pathogenesis, treatment, and prognosis of MPCs associated with breast and gynecologic cancers. It provides new intervention and treatment ideas for patients with BC-associated MPCs to improve quality of life and prognosis.

show abstract

“…The prognosis of EC is rather favorable, as about 75% of cases are diagnosed in an early stage and can be cured by surgery and in more advanced cases by additional radiotherapy and/or chemotherapy [ 2 ] resulting in a general five-year cancer-specific survival of around 80% for all stages and histological types [ 1 , 2 ]. The majority of EC (85%) known as the so-called type 1 cancers develop due to prolonged exposure to endogenous or exogenous estrogens in the absence of sufficient progestogen activity [ 3 , 4 , 5 ]. These type 1 EC are hormone-dependent and can be treated in early stages without surgery by endocrine manipulation, including estrogen withdrawal and/or high dose progestogens in premenopausal women who have not yet completed their families.…”

Section: Introductionmentioning

confidence: 99%

The Role of Gonadotropin-Releasing Hormone (GnRH) in Endometrial Cancer

Emons

Gründker

2021

Cells

Self Cite

View full text Add to dashboard Cite

Endometrial cancer (EC) is one of the most common gynecological malignancies. Gonadotropin releasing hormone (GnRH) is a decapeptide first described to be secreted by the hypothalamus to regulate pituitary gonadotropin secretion. In this systematic review, we analyze and summarize the data indicating that most EC express GnRH and its receptor (GnRH-R) as part of an autocrine system regulating proliferation, the cell cycle, and apoptosis. We analyze the available data on the expression and function of GnRH-II, its putative receptor, and its signal transduction. GnRH-I and GnRH-II agonists, and antagonists as well as cytotoxic GnRH-I analogs, have been shown to inhibit proliferation and to induce apoptosis in human EC cell lines in pre-clinical models. Treatment with conventional doses of GnRH-agonists that suppress pituitary gonadotropin secretion and ovarian estrogen production has become part of fertility preserving therapy of early EC or its pre-cancer (atypical endometrial hyperplasia). Conventional doses of GnRH-agonists had marginal activity in advanced or recurrent EC. Higher doses or more potent analogs including GnRH-II antagonists have not yet been used clinically. The cytotoxic GnRH-analog Zoptarelin Doxorubicin has shown encouraging activity in a phase II trial in patients with advanced or recurrent EC, which expressed GnRH-R. In a phase III trial in patients with EC of unknown GnRH-R expression, the cytotoxic GnRH doxorubicin conjugate was not superior to free doxorubicin. Further well-designed clinical trials exploiting the GnRH-system in EC might be useful.

show abstract

Tamoxifen and Endometrial Cancer: A Janus-Headed Drug

Cited by 54 publications

References 49 publications

Investigation of the Antitumor Effects of Tamoxifen and Its Ferrocene-Linked Derivatives on Pancreatic and Breast Cancer Cell Lines

Investigation of the Antitumor Effects of Tamoxifen and Its Ferrocene-Linked Derivatives on Pancreatic and Breast Cancer Cell Lines

Common Multiple Primary Cancers Associated With Breast and Gynecologic Cancers and Their Risk Factors, Pathogenesis, Treatment and Prognosis: A Review

The Role of Gonadotropin-Releasing Hormone (GnRH) in Endometrial Cancer

Contact Info

Product

Resources

About