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Nuclear Receptor Coactivators: Mechanism and Therapeutic Targeting in Cancer
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Andrew Cannon, Christopher Thompson, Rakesh Bhatia, Sushil Kumar
Given their ability to potentiate the function of various nuclear receptors, several nuclear receptor coactivators have been shown to play critical roles in the development and progression of cancer. While most of the work regarding the function of nuclear receptor coactivators in cancer has been conducted in the setting of hormone sensitive cancers, a significant body of literature exists for cancers that are not classically associated with hormone sensitivity. In the following section, we address the role of several nuclear receptor co-activator in hormone sensitive and hormone insensitive cancers (Table 1).
Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Goserelin is a synthetic decapeptide gonadorelin agonist analog (molecular weight, 1,269.41), first synthesized and patented by (the then) ICI in 1977 and now marketed by AstraZeneca as ZoladexTM (Figure 8.26). It was approved by the FDA in 1989 for the treatment of prostate cancer, and is now used worldwide to treat hormone-sensitive cancers of the prostate and breast (i.e., ER+ve in pre- and perimenopausal women), and some benign gynecological disorders (e.g., endometriosis, uterine fibroids, and endometrial thinning). For prostate cancer it is used for locally advanced disease as an alternative to surgical castration, adjuvant treatment to radiotherapy or radical prostatectomy in patients with high-risk localized or locally advanced prostate cancer, neoadjuvant treatment prior to radiotherapy in patients with high-risk localized or locally advanced prostate cancer and metastatic disease. It is also used for advanced breast cancer and ER+ve early breast cancer. It is also used in assisted reproduction and gender change treatments. Goserelin is now off-patent, and several generic versions are available.
Monographs of Topical Drugs that Have Caused Contact Allergy/Allergic Contact Dermatitis
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
Estradiol is a naturally occurring hormone that circulates endogenously within the human body. It is the most potent form of mammalian estrogenic steroids and acts as the major female sex hormone. As such, estradiol plays an essential role in the regulation of the menstrual cycle, in the development of puberty and secondary female sex characteristics, as well as in ageing and several hormonally-mediated disease states. Estradiol and estradiol esters (esterification of estradiol aims to improve absorption and bioavailability after oral administration or to sustain release from depot intramuscular injections) are commercially available in oral, transdermal, and injectable hormone therapy products for managing conditions associated with reduced estrogen production such as menopausal and peri-menopausal symptoms as well as hypoestrogenism. It is also used in transgender hormone therapy, as a component of oral contraceptive pills for preventing pregnancy (most commonly as ethinylestradiol), and is sometimes used for the palliative treatment of some hormone-sensitive cancers like breast and prostate cancer (1).
Dietary Glycemic Index and Glycemic Load and the Risk of Prostate Cancer: An Updated Systematic Review and Dose–Response Meta-Analysis
Published in Nutrition and Cancer, 2020
Alireza Sadeghi, Omid Sadeghi, Mahmoud Khodadost, Aliyar Pirouzi, Banafsheh Hosseini, Ahmad Saedisomeolia
Prostate cancer is a common disorder in men which is associated with a high morbidity and mortality (28–30). A combination of genetic and environmental factors, particularly diet, is involved in the etiology of cancer (28,31,32). Among dietary factors, a great attention has been given on dietary GI and GL (33). However, due to the discrepancy in available findings, there was no definite conclusion on the association of GI and GL with the prostate cancer. Based on the current meta-analysis, we found a significant positive dose–response association between dietary GI and the risk of prostate cancer, which is in the opposite of previous meta-analysis published in 2015 reporting no significant association (21). The mentioned meta-analysis, has not reported any dose–response results and only compared the individuals in the highest category of GI with those in the lowest category. When we did such comparison in our study, a positive non-significant association between GI and prostate cancer was seen. However, this association was only significant when we considered case–control studies or the studies conducted in non-US countries. In addition, studies on other hormone-sensitive cancers showed similar results. In a meta-analysis conducted by Schlesinger et al., a significant positive association was reported between dietary GI and the breast cancer (34). The similar finding was reported on ovarian cancer, as it is reported there is a positive significant association between GI and ovarian cancer risk (35).
Vulvovaginal atrophy in women after cancer
Published in Climacteric, 2019
Dehydroepiandrosterone is an inactive precursor for intracellular formation of androgens and estrogens, both premenopausally and postmenopausally. It is therefore a potential vaginal therapy for the symptoms of VVA. There have been a number of randomized controlled trials of dehydroepiandrosterone for VVA46 which showed a rapid correction of symptoms and signs with 6.5 mg of prasterone inserted vaginally daily, as well as improving sexual health. However, women with hormone-sensitive cancers were excluded and further studies on long-term safety data are needed in women with cancer. This may be an option after individualized discussion and consent; at present, the European Medicines Agency has contraindicated the use of this product in women with breast cancer but the US Food and Drug Administration has only advised caution.
Severity of hot flushes is inversely associated with dietary intake of vitamin B6 and oily fish
Published in Climacteric, 2019
T. Odai, M. Terauchi, A. Hirose, K. Kato, M. Akiyoshi, N. Miyasaka
Pharmaceutical therapies for VMS include hormone therapy, antidepressants, anticonvulsants, and anticholinergics. However, due to growing concern for the side effects of hormone therapy, especially in patients with hormone-sensitive cancer, such as breast and uterus cancer, research has turned to the effects of nutraceutical approaches on VMS. For example, a wide range of studies have been performed on the effects of the intake of phytoestrogens, including soy isoflavone, red clover, and lignan, on the frequency and severity of VMS12–18. However, the effects of the dietary intake of nutrients on VMS have not yet been fully elucidated. The aim of this study is therefore to investigate the relationships between the severity of HF and NS and the dietary intake of a variety of nutrients and food items in Japanese middle-aged women.