Advances in hormonal therapies for hormone naïve and castration-resistant prostate cancers with or without previous chemotherapy

Abstract

Hormonal manipulation plays a significant role in the treatment of advanced hormone naïve prostate cancer and castration-resistant prostate cancer (CRPC) with or without previous chemotherapy. Combination of gonadotropin releasing hormone (GnRH) agonists and androgen receptor (AR) antagonists (combined androgen blockade; CAB) is the first line therapy for advanced hormone naïve prostate cancer, but current strategies are developing novel GnRH antagonists to overcome disadvantages associated with GnRH agonist monotherapy and CAB in the clinical setting. Abiraterone acetate and enzalutamide are hormonal agents currently available for patients with CRPC and are both shown to improve overall survival versus placebo. Recently, in clinical trials, testosterone has been administered in cycles with existing surgical and chemical androgen deprivation therapies (ADT) (intermittent therapy) to CRPC patients of different stages (low risk, metastatic) to abate symptoms of testosterone deficiency and reduce cost of treatment from current hormonal therapies for patients with CRPC. This review will provide an overview on the therapeutic roles of hormonal manipulation in advanced hormone naïve and castration-resistant prostate cancers, as well as the development of novel hormonal therapies currently in preclinical and clinical trials.

Qianlie Xiaozheng Decoction Induces Autophagy in Human Prostate Cancer Cells via Inhibition of the Akt/mTOR Pathway

“…The primary PCa is almost the typical HDPC, androgen is the key growth factor of which, and androgen deprivation therapy shows obvious effects at the beginning of treatment. As the course of the PCa progresses after 14–30 months, most patients develop HIPC and eventually die from it, which is the final form and inevitable result of the development of PCa, and there is currently no effective treatment or cure ( Thy et al, 2015 ; Raymond et al, 2017 ). Among the various PCa cells, androgen-refractory PC3 and DU 145 cells are widely used in HIPC research.…”

“…Prostate cancer is one of the most prevalent malignant tumors as well as the second leading cause of cancer-related deaths in men in Western countries, with appropriately 15% of men having PCa during their lifetime ( Kar et al, 2016 ). Androgen deprivation therapy, a treatment for PCa, shows obvious effects at the beginning of treatment, but after 14–30 months, most patients develop HIPC ( Thy et al, 2015 ; Raymond et al, 2017 ). The median survival for HIPC patients is less than 20 months, and there is currently no effective treatment or cure ( Raymond et al, 2017 ).…”

Fighting tubulin-targeting anticancer drug toxicity and resistance

“…Since prostate cancer is in most cases initially androgen sensitive, for these patients and for patients with a disseminated disease at the time of diagnosis, androgen deprivation by surgical or chemical castration is the treatment of choice (Amaral et al 2012). Androgen deprivation can be achieved surgically, by orchiectomy, or chemically by targeting the androgen receptor (AR) pathway, either desensitizing it with luteinizing hormone-releasing hormone (LHRH) agonists or blocking it by LHRH antagonists or by antagonists of the AR (Pham et al 2016). Androgen deprivation therapy is quite effective in inducing apoptosis of hormonedependent cancer cells, resulting in tumor regression.…”

Angiogenesis Inhibition in Prostate Cancer: An Update

“…Advancement of clinical research over the last two decades, along with the approval of several targeted and immunomodulatory agents, together with chemotherapeutic agents such as docetaxel, prednisone, and mitoxantrone, have substantially changed the treatment landscape of metastatic CRPC (mCRPC). Although these agents have shown significant benefits to a percentage of patients, these benefits are short-lived [ 9 , 10 , 11 , 12 , 13 ]. Accordingly, there is a constant need to identify newer and better treatments that can be used alone or in combination with currently available therapies for better disease management and outcomes.…”