Integrative hyperthermia treatments for different types of cancer
Clifford L. K. Pang, Kaiman Lee in Hyperthermia in Oncology, 2015
Prostate cells without androgen stimulations will undergo apoptosis. Any treatment of androgen activity inhibition may be referred to as androgen deprivation therapy. Deprivation of androgen is primarily through the following strategies: (1) inhibition of testosterone secretion: surgical castration or medical castration (luteinizing hormone–releasing hormone analogs [LHRH-A]). (2) Block combination of androgen with receptor: application of antiandrogen drugs competitively closes the combination of androgen and prostate cells androgen receptor. The combination of the two can achieve the purpose of maximum androgen blockage. Other strategies include inhibition of adrenal gland source androgen synthesis as well as inhibition of the conversion of testosterone to dihydrotestosterone, and so on. Endocrine therapy aims to reduce the concentration of androgen in the body, inhibit adrenal gland source androgen synthesis, inhibit the conversion of testosterone to dihydrotestosterone, and block the combination of androgen with its receptor so as to suppress or control prostate cancer cell growth. Endocrine therapy methods include the following: castration, maximum androgen blockage, intermittent hormonal therapy, neoadjuvant endocrine therapy before radical treatment, and adjuvant endocrine therapy.
Endocrine Therapies
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
This agent has a unique dual mechanism of action, acting as both an androgen receptor antagonist and an inhibitor of CYP17A1, an enzyme required for the biosynthesis of androgens. In 2014 the company announced positive interim results from a Phase 2 study (i.e., ARMOR2), with data showing clinically meaningful reductions in PSA levels. This led to Phase III clinical trials (i.e., ARMOR3-SV) in AR-V7-expressing metastatic castration-resistant prostate cancer patients, comparing galeterone to enzalutamide. However, the trial was discontinued in 2016 when a Data Monitoring Committee determined that clinical endpoints were unlikely to be met. In 2018, it was announced that the agent would continue to be developed through a collaboration between Educational & Scientific LLC (ESL) and the University of Maryland Ventures.
Urinary tract disorders
Henry J. Woodford in Essential Geriatrics, 2022
Patients with distant metastases have a poor prognosis, with mean survival times of between 24 and 48 months.147 Anti-androgen treatment (e.g. bilateral orchidectomy or gonadorelin analogues) is indicated. Around 75% of men will have some symptomatic relief from this (e.g. reduced bone pain).147 Adverse effects of anti-androgen treatments include fatigue, depression, erectile dysfunction and hot flushes. They are also associated with an increased risk of osteoporosis. Other effects of long-term treatment may include an increased risk of vascular disease and diabetes.150 The addition of the chemotherapy drug, docetaxel, to antiandrogen therapy may have a survival benefit for selected men aged over 70.151 The antiandrogen drugs, abiraterone or enzalutamide, may be used in men with prostate cancer who are unsuitable for other chemotherapy. Surgery (radical prostatectomy) and radiotherapy may be appropriate in some men with high-grade tumours.
Cancer epigenetics and the potential of epigenetic drugs for treating solid tumors
Published in Expert Review of Anticancer Therapy, 2019
Zhenghui Liu, Yingxue Gao, Xiong Li
The progression of many cancers depends on aberrant hormone metabolism or the mutation of hormone receptors, for example the mutation of estrogen/estrogen receptor in breast cancer and androgen/androgen receptor in prostate cancer. Hormone antagonists or inhibitors of hormone receptors have become the first-in-class therapeutics for these cancer types. However, cancer patients inevitably develop drug resistance after treatment and epigenetic changes have been identified as a key element for drug resistance. Epigenetic drugs may, therefore, overcome cancer resistance to hormonal drugs. Vorinostat and Bicalutamide, an androgen receptor antagonist, had a synergistic effect on cell proliferation and apoptosis induction in prostate cancer cell lines. In a phase II clinical trial, the combination of these two drugs followed by radical prostatectomy decreased the tumor size of primary prostate cancer [99,100]. A triple combination of TSA, Bicalutamide and Finasteride (a 5α-reductase inhibitor) targeting the androgen pathway had synergistic effects inducing prostate cancer cell apoptosis [101]. Azacytidine plus TSA and Diarylpropionitrile (DPN, a highly potent ERβ agonist) displayed strong anticancer effects, inducing apoptosis and decreasing proliferation in prostate cancer cells, along with downregulation of Cyclin D1 and VEGF [94].
Evaluation of the efficacy of an antioxidant combination for the modulation of metabolic, endocrine, and clinical parameters in patients with polycystic ovary syndrome
Published in Gynecological Endocrinology, 2023
Carmen Pingarrón Santofímia, Silvia Poyo Torcal, Helena López Verdú, Alexandra Henríquez Linares, Virginia Calvente Aguilar, Pablo Terol Sánchez, María Sol Martínez García, Pilar Lafuente González
In our study, a significant improvement of clinical and analytical indicators after 6 months of treatment with ALA + NAC + B6+SAMe can be associated with a dual mechanism of action: increasing insulin sensitivity through de novo synthesis of glutathione and modulating androgen action by improving DNA methylation by SAMe. Regarding the first mechanism, the regulation of insulin action depends on hepatic glutathione content. Modulating de novo synthesis of glutathione would help in the prevention of diabetes, as glutathione can block the glucose/reactive oxygen species-induced β-cell damages [18, 19]. With respect to the second mechanism, it is known that the promoter region of the androgen receptor is hypo-methylated in granulosa cells of women with PCOS [20]. In addition, granulosa cells isolated from PCOS patients show a 25% reduction in the level of 5-methylcytosine [21]. DNA methylation is catalyzed by a family of DNA methyltransferases that transfer a methyl group from SAMe to the fifth carbon of a cytosine residue to form 5-methylcytosine [22]. This could be related to the antiandrogen response seen in the present study. However, further investigation is required to elucidate the potential of SAMe in epigenetic modulation of the pathogenesis of PCOS.
The cellular and molecular effects of the androgen receptor agonist, Cl-4AS-1, on breast cancer cells
Published in Endocrine Research, 2018
Mamoun Ahram, Ebtihal Mustafa, Shatha Abu Hammad, Mariam Alhudhud, Randa Bawadi, Lubna Tahtamouni, Faisal Khatib, Malek Zihlif
In recent years, attention has been directed toward alternative therapeutic targets. One such target is androgen receptor (AR). In fact, androgen therapy was a strategy of treating breast cancer decades ago till the emergence of targeted therapeutics such as SERMs9 and inhibitors of androgen aromatization into estrogen.11 There has recently been a revival of utilizing antiandrogen therapy due to a number of reasons. First of all, breast cancer is a heterogeneous disease with multiple subclasses, one of which is characterized by active AR signaling pathway and, hence, known a luminal AR and is represented by molecular apocrine breast cancer.9 In addition, AR is expressed in all subtypes of breast cancer, although the extent of expression varies according to the type.12 For example, up to 90% of luminal breast cancer is found to be AR-positive, relative to 32% of basal-like breast cancer.12 In fact, AR expression is associated with better prognosis of the disease12,13, although it has been suggested that it can also act as an oncogene in ER-negative breast cancers.14,15 It has been shown that treatment of TNBC cells with AR antagonists reduces cell proliferation.16 On the other hand, contradictory results have been reported on the effect of AR agonists on breast cancer cells (for review, see11,17). Nevertheless, clinical trials have shown promising results in treating breast cancer patients.18