PURPOSE: Metastatic prostatic adenocarcinoma can be controlled by androgen ablation through the active process of programmed cell death in androgen responsive cells. However, about 20-30% of patients have no clinical response to androgen withdrawal. Because of the importance of apoptosis in effecting tumor control, factors involved in this process may be helpful in predicting androgen insensitivity. So, we evaluated the significance of bcl-2 protooncogene expression pattern with therapeutic response of prostatic cancer MATERIALS AND METHODS: We examined the cellular expression of bel-2 protein using immunohistochemical stain in tumor samples from 40 patients with metastatic prostatic cancer(stage D) and determined whether expression of blc-2 protein has related to the therapeutic response of prostatic cancer. RESULTS: The hormonal status of the patient's tumor was determined by the clinical response to therapy. Androgen independent cancer was defined as that subset of patients who experienced no initial response to androgen ablation, or who experienced disease relapse following an initial response to androgen ablation. So, we found that androgen dependent prostatic cancer was 22 patients and androgen independent prostatic cancer was 18 patients. The positive staining for bcl-2 was 27.3%(6/22) and 83.3%(15/18) in androgen dependent and independent prostatic cancer, respectively. It was significant difference(p<0.05). CONCLUSIONS: These results suggest that bcl-2 expression is associated with androgen independent prostatic cancer and used one of the factors to predict which patient with prostatic cancer will respond to androgen ablation.
Adenocarcinoma ; Apoptosis ; Cell Death ; Humans ; Prostate* ; Prostatic Neoplasms* ; Prostatic Neoplasms, Castration-Resistant ; Recurrence

Androstenes ; Docetaxel ; Humans ; Male ; Prednisone ; Prostatic Neoplasms ; Prostatic Neoplasms, Castration-Resistant

This is a case report of 3 patients who had a dramatic and long-term complete response after antiandrogen withdrawal. All 3 patients were diagnosed with advanced or metastatic prostate cancer with a high prostate-specific antigen (PSA) level. For all patients, we started combined androgen blockade as androgen deprivation therapy and the PSA concentration decreased to <0.1 ng/mL, but then started to increase. After discontinuation of antiandrogen the PSA concentration decreased again and has remained below the limit of sensitivity for more than 1 year in all 3 patients.
Androgen Antagonists ; Humans ; Prostate ; Prostate-Specific Antigen ; Prostatic Neoplasms ; Prostatic Neoplasms, Castration-Resistant

Male ; Humans ; Prostatic Neoplasms/pathology* ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Hormones ; Androgen Antagonists/therapeutic use*

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.
Male ; Humans ; Prostatic Neoplasms/pathology* ; Androgen Antagonists/therapeutic use* ; Prostate-Specific Antigen ; Castration ; Prostatic Neoplasms, Castration-Resistant/drug therapy*

Prostate cancer is the most common malignancy in the reproductive system of older males. Androgen deprivation therapy (ADT) is an important treatment for prostate cancer patients. However, almost all prostate cancer patients unavoidably progress to the castration-resistant stage after ADT treatment. Recent studies have shown that tumor-associated immune cells play major roles in the initiation, progression, and metastasis of prostate cancer. Various phenotypes of tumor-associated immune cells have tumor-promoting or antitumor functions mediated by interacting with tumor cells. Here, we review the current knowledge of tumor-associated immune cells in prostate cancer.
Disease Progression ; Humans ; Lymphocytes, Tumor-Infiltrating/pathology* ; Macrophages/pathology* ; Male ; Neutrophils/pathology* ; Prostatic Neoplasms/therapy* ; Prostatic Neoplasms, Castration-Resistant/therapy*

Most prostate cancer cases ultimately relapse after a period of initial response to castration therapy and progress to intractable castration-resistant prostate cancer (CRPC). Hardly any therapeutic options currently used can improve the 2- to 3-year survival of the patient. Recently, some new drugs for the treatment of CRPC through various action mechanisms have been approved, and others are in the advanced stage of clinical trial. This review provides an overview of these new therapeutic agents.
Antineoplastic Agents ; therapeutic use ; Humans ; Male ; Neoplasm Recurrence, Local ; Orchiectomy ; Prostatic Neoplasms ; surgery ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; mortality

Androgen receptor (AR), a hormonal transcription factor, plays important roles during prostate cancer progression and is a key target for therapeutic interventions. While androgen-deprivation therapies are initially successful in regressing prostate tumors, the disease ultimately comes back as castration-resistant prostate cancer (CRPC) or at the late stage as neuroendocrine prostate cancer (NEPC). CRPC remains largely dependent on hyperactive AR signaling in the milieu of low androgen, while NEPC is negative of AR expression but positive of many AR-repressed genes. Recent technological advances in genome-wide analysis of transcription factor binding sites have revealed an unprecedented set of AR target genes. In addition to its well-known function in activating gene expression, AR is increasingly known to also act as a transcriptional repressor. Here, we review the molecular mechanisms by which AR represses gene expression. We also summarize AR-repressed genes that are aberrantly upregulated in CRPC and NEPC and represent promising targets for therapeutic intervention.
Epigenetic Repression ; Humans ; Male ; Prostatic Neoplasms, Castration-Resistant/genetics* ; Receptors, Androgen/genetics* ; Transcriptional Activation

ARAMIS is an international Phase III trial demonstrating the beneficial role of darolutamide, a novel anti-androgen that has been found to prolong metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer. Darolutamide is a novel nonsteroidal androgen receptor antagonist that has unique structurally distinct properties with low blood–brain barrier penetration that was shown to improve metastasis-free survival by 22 months compared to placebo (40.4 months vs 18.4 months), reducing the risk of metastasis or death by 59%. Darolutamide also showed improvement in secondary and exploratory endpoints including progression-free survival, prolonged time to PSA progression, PSA response and time to initiating additional antineoplastic therapy, time to pain progression, and time to cytotoxic chemotherapy, but overall survival is not yet reached in either the darolutamide or the placebo arm. Adverse events leading to trial discontinuation were similar at 8.9% and 8.7% in the darolutamide and placebo arms, respectively. Darolutamide was filed as a new drug application to the United States Food and Drug Administration (US FDA) for use in the setting of nonmetastatic castration-resistant prostate cancer.
Androgen Receptor Antagonists ; Androgens ; Humans ; Male ; Prostatic Neoplasms, Castration-Resistant ; Pyrazoles

Reprogramming of metabolism is a hallmark of tumors, which has been explored for therapeutic purposes. Prostate cancer (PCa), particularly advanced and therapy-resistant PCa, displays unique metabolic properties. Targeting metabolic vulnerabilities in PCa may benefit patients who have exhausted currently available treatment options and improve clinical outcomes. Among the many nutrients, glutamine has been shown to play a central role in the metabolic reprogramming of advanced PCa. In addition to amino acid metabolism, glutamine is also widely involved in the synthesis of other macromolecules and biomasses. Targeting glutamine metabolic network by maximally inhibiting glutamine utilization in tumor cells may significantly add to treatment options for many patients. This review summarizes the metabolic landscape of PCa, with a particular focus on recent studies of how glutamine metabolism alterations affect therapeutic resistance and disease progression of PCa, and suggests novel therapeutic strategies.
Male ; Humans ; Glutamine/therapeutic use* ; Prostatic Neoplasms, Castration-Resistant/drug therapy*