-
European Journal of Pharmacology Jan 2020The development of targeted therapies has been a consistent goal for hormone-related diseases treatment. As a result of increased knowledge of the role of androgens in... (Review)
Review
The development of targeted therapies has been a consistent goal for hormone-related diseases treatment. As a result of increased knowledge of the role of androgens in different diseases, anti-androgen treatment is becoming increasingly important in targeted therapy. Androgens play an important role in different disorders, therefore, androgen receptor signalling is a crucial factor in pathological conditions. The androgen receptor is a transcription factor activated by the testosterone metabolite 5α-dihydrotestosterone and regulates the expression of genes related to sexual differentiation, growth and survival of prostate cells, and to a certain extent, cancer progression. Herein, we review anti-androgen therapies in cancer and other selected diseases and provide examples where anti-androgen drugs can be used as both main and supportive treatments in the multimodal therapeutic scheme. Even in diseases with low serum levels of testosterone or DHT, anti-androgen therapy plays an important role in new treatments. Therefore, the use of anti-androgens is an appealing strategy in which to overcome resistance to primary treatment by assuring better therapy results. In this review, we take into account both older generation hormonal drugs and the new drug classes. Additionally, we review recent studies that suggest new anti-androgen agents have not entirely replaced some of the old standards.
Topics: Androgen Antagonists; Androgens; Animals; Hormone Replacement Therapy; Humans; Neoplasms
PubMed: 31712062
DOI: 10.1016/j.ejphar.2019.172783 -
Journal of Nuclear Medicine : Official... Aug 2022A subset (35%) of triple-negative breast cancers (TNBCs) expresses androgen receptor (AR) activity. However, clinical trials with antiandrogen drugs have shown limited...
A subset (35%) of triple-negative breast cancers (TNBCs) expresses androgen receptor (AR) activity. However, clinical trials with antiandrogen drugs have shown limited efficacy, with about a 19% clinical benefit rate. We investigated the therapeutic enhancement of antiandrogens as radiosensitizers in combination with F-FDG in TNBC. We screened 5 candidate drugs to evaluate shared toxicity when combined with either F-FDG, x-rays, or ultraviolet radiation, at doses below their respective half-maximal inhibitory concentrations. Cytotoxic enhancement of antiandrogen in combination with F-FDG was evaluated using cell proliferation and DNA damage assays. Finally, the therapeutic efficacy of the combination treatment was evaluated in mouse tumor models of TNBC and prostate cancer. Bicalutamide, an antiandrogen drug, was found to share similar toxicity in combination with either F-FDG or x-rays, indicating its sensitivity as a radiosensitizer to F-FDG. Cell proliferation assays demonstrated selective toxicity of combination bicalutamide-F-FDG in AR-positive 22RV1 and MDA-MB-231 cells in comparison to AR-negative PC3 cells. Quantitative DNA damage and cell cycle arrest assays further confirmed radiation-induced damage to cells, suggesting the role of bicalutamide as a radiosensitizer to F-FDG-mediated radiation damage. Animal studies in MDA-MB-231, 22RV1, and PC3 mouse tumor models demonstrated significant attenuation of tumor growth through combination of bicalutamide and F-FDG in the AR-positive model in comparison to the AR-negative model. Histopathologic examination corroborated the in vitro and in vivo data and confirmed the absence of off-target toxicity to vital organs. These data provide evidence that F-FDG in conjunction with antiandrogens serving as radiosensitizers has utility as a radiotherapeutic agent in the ablation of AR-positive cancers.
Topics: Androgen Antagonists; Animals; Cell Line, Tumor; Fluorodeoxyglucose F18; Humans; Mice; Nitriles; Radiation-Sensitizing Agents; Receptors, Androgen; Triple Negative Breast Neoplasms; Ultraviolet Rays
PubMed: 34772792
DOI: 10.2967/jnumed.121.262958 -
Asian Journal of Andrology 2021Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists and antagonists is the mainstay of advanced prostate cancer treatment. Both drug... (Review)
Review
Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists and antagonists is the mainstay of advanced prostate cancer treatment. Both drug classes decrease levels of luteinizing hormone and follicle-stimulating hormones (FSH), thereby lowering testosterone to castrate levels. This is associated with adverse events (AEs), including cardiovascular (CV) disorders, bone fractures, metabolic dysfunction, and impaired cognitive function. This literature review discusses these AEs, with a focus on CV and bone-related events. A hypothesis-generating meta-analysis of six clinical trials showed a potentially increased risk for CV disorders with GnRH agonists versus the GnRH antagonist degarelix. While no study has directly compared GnRH agonists versus antagonists with a primary CV outcome, one hypothesis for this observation is that GnRH agonists lead to initial surges in FSH that may negatively impact CV health, whereas antagonists do not. GnRH agonists are associated with metabolic and cognitive AEs and while data are lacking for GnRH antagonists, no differences in risk are predicted. Other common AEs with ADT include injection site reactions, which are much more common with degarelix than with GnRH agonists, which may reflect differing administration and injection techniques. Future studies are needed to further evaluate and compare the safety profiles of GnRH agonists and antagonists, especially in patients with pre-existing CV disease and other co-morbidities. Physicians should carefully evaluate benefits and risks when prescribing ADT and ensure that side effects are well managed.
Topics: Androgen Antagonists; Gonadotropin-Releasing Hormone; Humans; Male; Prostatic Neoplasms
PubMed: 32655041
DOI: 10.4103/aja.aja_22_20 -
Endocrine-related Cancer Dec 2017Prostate cancer is the most common newly diagnosed malignancy in men, and the second most common cause of cancer-related death in the United States. The primary... (Review)
Review
Prostate cancer is the most common newly diagnosed malignancy in men, and the second most common cause of cancer-related death in the United States. The primary treatment for recurrent prostate cancer is androgen deprivation, and this therapy is typically continued lifelong for patients with metastatic prostate cancer. Androgens and androgen deprivation have profound effects on the immune system, a finding that has become more appreciated in an era where immune-based treatments for cancer are being increasingly explored. Preclinical studies suggest that androgen deprivation could potentially positively or negatively affect the use of approved immunotherapies, or those that are being developed for the treatment of prostate cancer. In this review, we provide a brief overview of the different types of androgen deprivation treatments used in the management of prostate cancer, discuss their effects on prostate tumors and the immune system and how they are being explored in combination with immunotherapy. Finally, we address some of the critical questions in the field that must be answered to identify the best approaches to combine androgen deprivation with immunotherapy for the treatment of prostate cancer.
Topics: Androgen Antagonists; Humans; Immunotherapy; Male; Prostatic Neoplasms
PubMed: 28814451
DOI: 10.1530/ERC-17-0145 -
Current Oncology Reports Feb 2017Prostate cancer is the second leading cause of cancer deaths in the USA. The challenge in managing castration-resistant prostate cancer (CRPC) stems not from the lack of... (Review)
Review
Prostate cancer is the second leading cause of cancer deaths in the USA. The challenge in managing castration-resistant prostate cancer (CRPC) stems not from the lack of therapeutic options but from the limited duration of clinical and survival benefit offered by treatments in this setting due to primary and acquired resistance. The remarkable molecular heterogeneity and tumor adaptability in advanced prostate cancer necessitate optimization of such treatment strategies. While the future of CRPC management will involve newer targeted therapies in deliberately biomarker-selected patients, interventions using current approaches may exhibit improved clinical benefit if employed in the context of optimal sequencing and combinations. This review outlines our current understanding of mechanisms of therapeutic resistance in progression to and after the development of castration resistance, highlighting targetable and reversible mechanisms of resistance.
Topics: Androgen Antagonists; Biomarkers, Tumor; Disease Progression; Drug Resistance, Neoplasm; Humans; Male; Molecular Targeted Therapy; Prostatic Neoplasms, Castration-Resistant
PubMed: 28229393
DOI: 10.1007/s11912-017-0568-7 -
Archivos Espanoles de Urologia Dec 2023New-generation imaging techniques and the increasing use of surgery in high-risk prostate cancer (PCa) allow us to detect many cases of nodal disease at initial... (Review)
Review
BACKGROUND
New-generation imaging techniques and the increasing use of surgery in high-risk prostate cancer (PCa) allow us to detect many cases of nodal disease at initial diagnosis or after resection. The treatment of PCa with pathologic regional nodes has evolved from the exclusive use of systemic therapy to its combination with locoregional treatment. It can also represent a benefit in the overall survival. However, the evidence from randomised studies is limited. Thus, we review the most relevant results in this scenario.
MATERIALS AND METHODS
A literature search was conducted in MEDLINE, PubMed, EMBASE, Clinical-Trials.gov and Web of Science on January 2023 to review node-positive PCa by considering the relevant literature on this topic published with no restrictions on date and language. The search keywords used were "Prostatic Neoplasms" (MeSh) and "Node-positive" (Text Word) and "Radiotherapy" (MeSh) and ("Androgen Antagonists" (MeSh) or "Antineoplastic Agents, Hormonal" (MeSh)), which are indexed within the Medical Subject Headings database.
RESULTS
The management of node-positive PCa has no clear definitive consensus at the initial disease diagnosis or after surgery. However, in this review, we summarise the existing literature for the management of these patients in both scenarios, considering imaging tests, radiotherapy, hormone therapy and second-generation hormonal treatments.
CONCLUSIONS
The combination of radiotherapy and androgen-deprivation therapy is the treatment of choice. The addition of second-generation hormone therapy, plus the intensification of radiotherapy schedules, will likely change the treatment paradigm for these patients.
Topics: Male; Humans; Androgen Antagonists; Androgens; Prostatic Neoplasms; Consensus
PubMed: 38186065
DOI: 10.56434/j.arch.esp.urol.20237610.88 -
Annals of Palliative Medicine May 2021There has been growing interest in oligometastatic prostate cancer (OMPC) with a mounting body of evidence to suggest that it is a distinct disease state, both... (Review)
Review
There has been growing interest in oligometastatic prostate cancer (OMPC) with a mounting body of evidence to suggest that it is a distinct disease state, both biologically and prognostically, when compared to polymetastatic prostate cancer. Three subgroups have been recognised; de novo synchronous, metachronous/oligorecurrent and oligoprogressive disease. The belief that patients with OMPC can be treated more aggressively to improve survival is transforming patient care. Identifying these patients poses the first challenge, and we explore the imaging modalities currently utilised and those that are promising. For patients with de novo synchronous OMPC, both early systemic treatment in addition to androgen deprivation therapy (ADT) and radiotherapy to the prostate increase overall survival (OS), and both are increasingly being integrated into routine clinical practice. Metastasis-directed therapy (MDT) has predominantly been delivered using stereotactic body radiotherapy (SBRT) in prostate cancer and studies have shown SBRT is well-tolerated, provides excellent local control and can be used to delay ADT in the metachronous setting. We discuss the current management strategies in OMPC, review the evidence supporting the use of SBRT and outline ongoing trials.
Topics: Androgen Antagonists; Humans; Male; Prostatic Neoplasms; Radiosurgery
PubMed: 33752437
DOI: 10.21037/apm-20-1215 -
American Society of Clinical Oncology... May 2018There are 15.5 million cancer survivors in the United States because of, in part, improvements in therapy. As a result, there will be an increased burden of long- and... (Review)
Review
There are 15.5 million cancer survivors in the United States because of, in part, improvements in therapy. As a result, there will be an increased burden of long- and late-term complications of cancer care, such as metabolic alterations. These metabolic changes will include alterations in bone resorption, obesity, hypercholesterolemia, and diabetes mellitus. The majority of cancer treatment-related toxicities have focused on endocrine therapy; however, chemotherapy and supportive medications, such as steroids, contribute to the development of these disorders. Because of the chronicity of these metabolic changes and their impact on morbidity, cancer risk, and outcomes as well other negative effects, including musculoskeletal pain and vasomotor symptoms, alternative strategies must be developed. These strategies should include nonpharmacologic approaches. Here, we summarize metabolic changes secondary to cancer care and integrative approaches to help alleviate therapy-associated toxicities.
Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Brain Diseases, Metabolic; Combined Modality Therapy; Delivery of Health Care, Integrated; Disease Management; Glucocorticoids; Humans; Hypogonadism; Metabolic Syndrome; Neoplasms; Osteoporosis
PubMed: 30231327
DOI: 10.1200/EDBK_201411 -
Frontiers in Endocrinology 2023Studies using novel antiandrogens (NAA) in patients with metastatic castration-resistant prostate cancer (mCRPC) have shown overall survival benefit. As patients develop... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies using novel antiandrogens (NAA) in patients with metastatic castration-resistant prostate cancer (mCRPC) have shown overall survival benefit. As patients develop resistance to NAA therapy, the poly(ADP-ribose) polymerase inhibitor (PARPi) olaparib in combination with NAA may become a promising therapy. However the overall benefit of olaparib monotherapy or combination therapy still needs to be evaluated. Therefore, we performed a network meta-analysis to assess the efficacy and toxicity between olaparib, olaparib combined with abiraterone and NAA.
METHODS
We searched PubMed, EMBASE, the Cochrane Library and American Society of Clinical Oncology (ASCO) University Meeting abstracts for randomized controlled trials reporting olaparib and NAA from 2010 up to March, 2023. Network meta-analysis using Stata 16.0 and R 4.4.2, hazard ratios (HR) with 95% confidence intervals (CI) were used to assess the results.
RESULTS
Four trials reported olaparib, olaparib plus abiraterone and apalutamide plus abiraterone. radiographic progression-free survival (rPFS) was significantly lower in patients on apalutamide plus abiraterone compared to olaparib (HR, 1.43; 95% CI, 1.06-1.93). rPFS was similar for olaparib plus abiraterone and olaparib (HR, 1.35; 95% CI, 0.99-1.84); likewise, olaparib plus abiraterone and apalutamide plus abiraterone were similar (HR, 1.06; 95% CI, 0.83-1.35). In addition, there was no significant difference between the three interventions for OS. But olaparib has the highest probability of being a preferred treatment for improving rPFS and OS.
CONCLUSION
rPFS was in favor of olaparib compared with apalutamide plus abiraterone. But there were no difference between olaparib plus abiraterone and either olaparib or apalutamide plus abiraterone. Apalutamide plus abiraterone might be the most preferred intervention in cases where AEs are involved.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com, identifier INPLASY2023100072.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Antineoplastic Agents
PubMed: 38027160
DOI: 10.3389/fendo.2023.1225033 -
Lakartidningen Apr 2024There is a long history of curative treatment of prostate cancer. However, as prostate cancer often grows very slowly, and symptoms do not have time to develop during a... (Review)
Review
There is a long history of curative treatment of prostate cancer. However, as prostate cancer often grows very slowly, and symptoms do not have time to develop during a person's lifetime, a more tentative approach has become more and more common in many cases. This may be through either watchful waiting or active surveillance. In the first case palliative hormonal treatment is given in the case of progression, in the latter curative treatment would be the choice. When treatment is deemed necessary for localized disease, surgery and radiotherapy are considered equivalent in terms of efficacy and overall risk of side effects. For locally advanced disease, radiotherapy is the recommended first-hand choice outside the SPCG 15 study. Focal treatment, which may lead to less side effects than surgery or radiotherapy, is not recommended outside trial settings due to lack of long-term follow-up data.
Topics: Humans; Male; Prostatic Neoplasms; Watchful Waiting; Prostatectomy; Androgen Antagonists; Palliative Care
PubMed: 38650398
DOI: No ID Found