User:Areisdematos/ article draft

Hormonal Therapy (oncology): SERMS section editing

Hormone Receptor Antagonists

Hormone receptor antagonists bind to the normal receptor for a given hormone and prevent its activation. The target receptor may be on the cell surface, as in the case of peptide and glycoprotein hormones, or it may be intracellular, as in the case of steroid hormone receptors.

Selective estrogen receptor modulators/degradation[edit]

Selective estrogen receptor modulators (SERMs) are an important class of hormonal therapy agents which act as antagonists of the estrogen receptor and are used primarily for the treatment and chemoprevention of breast cancer. Estrogen receptors are steroid receptors that manage the reproduction of cells.^[1] Estrogen receptors have two different isoforms, ERα and ERβ^[2]. SERMS act as competitive antagonist; they block the binding site of the receptor by acting like the agonist but in the end when they bind the receptor is not not activated^[3].  When the SERMs bind to the ER, the helix 12 of the receptor undergoes changes based on if it's stimulated by an agonist or an antagonist.

• Tamoxifen

Some modulator members of this family, such as tamoxifen, are actually partial agonists, which can actually increase estrogen receptor signalling in some tissues, such as the endometrium. The protein NCOA1, influences Tamoxifen to act as an agonist to promote gene transcription for the endometrial cells^[4]. Tamoxifen is currently the first-line treatment for nearly all pre-menopausal women with hormone receptor-positive breast cancer. Tamoxifen's side chain blocks the helix 12 from capping the ligand binding domain and this action leads to the inhibition of the ERα signaling pathway in breast cancer cells(MCF7 cells)^[5]. A study was done where mice were injected with both, breast cancer cells and an endometrial cell line. After being treated with Tamoxifen the count for endometrial cell line increased and the breast cancer cells decreased.

• Raloxifene

Raloxifene, also known as Ketoxifene, is another partial agonist SERM which does not seem to promote endometrial cancer, and is used primarily for chemoprevention of breast cancer in high-risk individuals, as well as to prevent osteoporosis. Raloxifene's anatagonist abilities can be inhibited by changing the Nitrogen on it's side chain to a Carbon. This SERM can be used to inhibit Tamoxifen from having an effect on the endometrial cells, which can lead to possibly uterine cancer.

• Toremifene

Toremifene and fulvestrant are SERMs with little or no agonist activity, and are used for treatment of metastatic breast cancer. Toremifene works in a similar way as Tamoxifen. Toremifene is a nonsteroidal estrogen antagonist which blocks the estrogen receptors in the breat tissue. Although the effects, which are sweatiing, hot flashes, weakness, thromboembolic and gynecologic events, of both are similar the Toremifene is known to be the safer alternative. Since there is not much known about how effective this SERM truely is Tamoxifene is usually perscribed before given anything else like Toremifene.

Antiandrogens[edit]

Antiandrogens are a class of drugs which bind and inhibit the androgen receptor, which are steroid receptors,  blocking the growth- and survival-promoting effects of testosterone on certain prostate cancers.  Flutamide and bicalutamide are antiandrogens which are frequently used in the treatment of prostate cancer, either as long-term monotherapy, or in the initial few weeks of GnRH analog therapy.^[1] (See also Androgen deprivation therapy)

High levels of androgens also increases risks for postmenopausal women diagnosed with breast cancer. Concentrations of androgens can vary in pre-  and postmenopausal women. High testosterone in premenopausal leads to higher risks of BC. One of the reasons why it is believed that androgens play a part in breast cancer is because androgen receptors and ERalpha share the same coactivator. The coactivator for androgen receptors, ARA70, increases gene expression of ERalpa, which is the estrogen receptor subtype that is involved in BC. The antiandrogen, Casodex, prevents the resistance of Tamoxifen when in the presence of androgen receptors.

*I cannot add to the talk section so I'm just gonna add my comments down here:

·       I feel like you go into too much detail about competitive antagonists: I believe if anyone is reading this article, that are most likely familiar with the concept of competitive inhibition. I do not think you have to reiterate this in this article specifically

·       I believe you should however clarify what helix 12 is. 

·       I feel that the use of italics is unneeded and not common on Wikipedia.

·       I feel like you jump into the NCOA1 talk a bit too abruptly, I would work on making that either a separate section or making the flow of the part of the paragraph that talks about it more fluid.

·       I would make a separate section for tamoxifen/raloxifene/other drugs. The receptor talk should be its own section and the clinical info, ie studies, cell lines, etc should be a different section.

·       I do not think citing Gottardist et. al. explicitly is appropriate for this article. I would summarize their findings and cite them as normal, meaning I don’t think names have to be mentioned in the meat of the article

·       I also do not think it is appropriate to summarize the study in detail. You can paraphrase some of it a bit more.

·       The details about the elemental structure of the drug seem a little out of scope for the article to me.

·       Your section on Antiandrogens was very nice. You should follow this flow for the rest of your wiki contributions! Overall very nice job, very interesting content and valuable contributions to the page.

-Lexi