Androgen Ablation Combined with CTLA-4 Blockage-Based Immunotherapy as a Treatment for Prostate Cancer

2002 ◽  
Author(s):  
Eugene D. Kwon
Keyword(s):  
Prostate Cancer ◽  
Androgen Ablation

Paeonol Inhibits Prostate Cancer Cell Invasion and Epithelial-Mesenchymal Transformation by Inactivation of STAT3 Pathway

2020 ◽  
Vol 19 (1) ◽  
pp. 15-20
Author(s):  
Junyi Xiang ◽  
Feng Huang ◽  
Renhua Huang ◽  
Jingzhan Su ◽  
Yulong Liu
Keyword(s):  
Prostate Cancer ◽  
Treatment Options ◽  
Surrogate Marker ◽  
Cytotoxic Agents ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Ablation Therapy ◽  
Androgen Ablation ◽  
Mesenchymal Transformation ◽  
Dose Dependent

Prostate cancer is one of the leading causes of death in men all over the world. Treatment options such as androgen ablation therapy and cytotoxic agents have many undesirable side effects, narrow therapeutic windows, or other limitations. In this research, we have explored the effects of paeonol on prostate cancer and its mechanism of action. Our results have shown that paeonol reduced the viability of prostate cancer cells in a dose-dependent manner. The wound-healing assay, a surrogate marker of tumor metastasis, showed that the relative wound width of 10 µM group was less than that of 50 µM paeonol-treated cells. Besides, the results of the transwell assay also showed that the number of migrated cells was significantly lower after treatment with 50 µM paeonol compared to the 10 µM group. The Western blot results showed that paeonol treatment induced a decrease in the mesenchymal markers (vimentin and N-cadherin), while the epithelial marker (E-cadherin) increased in a dose-dependent manner suggesting that paeonol effectively inhibits the epithelial-mesenchymal transformation in PC3 cells. Furthermore, the expression of STAT3 and p-STAT3 was also decreased after paeonol treatment, which indicated that the STAT3 signaling pathway was inhibited by paeonol. To conclude, the results summarized in this paper suggest that paeonol could be a potential candidate in the treatment of prostate cancer.

scholarly journals Treating the patient and not just the cancer: therapeutic burden in prostate cancer

2021 ◽  
Author(s):  
Daniel E. Spratt ◽  
Neal Shore ◽  
Oliver Sartor ◽  
Dana Rathkopf ◽  
Kara Olivier
Keyword(s):  
Prostate Cancer ◽  
Second Generation ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Patient Treatment ◽  
Free Survival ◽  
Androgen Ablation ◽  
Therapeutic Benefits ◽  
Age Related ◽  
Concomitant Medications

Abstract Background Prostate cancer (PC) is a leading cause of death in older men. Androgen deprivation therapy (ADT) is considered the standard-of-care for men with locally advanced disease. However, continuous androgen ablation is associated with acute and long-term adverse effects and most patients will eventually develop castration-resistant PC (CRPC). The recent approval of three, second-generation androgen receptor inhibitors (ARIs), apalutamide, enzalutamide, and darolutamide, has transformed the treatment landscape of PC. Treatment with these second-generation ARIs have produced positive trends in metastasis-free survival, progression-free survival, and overall survival. For patients with non-metastatic CRPC, who are mainly asymptomatic from their disease, maintaining quality of life is a major objective when prescribing therapy. Polypharmacy for age-related comorbidities also is common in this population and may increase the potential for drug–drug interactions (DDIs). Method This review summarizes the multiple factors that may contribute to the therapeutic burden of patients with CRPC, including the interplay between age, comorbidities, concomitant medications, the use of ARIs, and financial distress. Conclusions As the treatment landscape in PC continues to rapidly evolve, consideration must be given to the balance between therapeutic benefits and potential treatment-emergent adverse events that may be further complicated by DDIs with concomitant medications. Patient-centered communication is a crucial aspect of alleviating this burden, and healthcare professionals (HCPs) may benefit from training in effective patient communication. HCPs should closely and frequently monitor patient treatment responses, in order to better understand symptom onset and exacerbation. Patients also should be encouraged to participate in exercise programs, and health information and support groups, which may assist them in preventing or mitigating certain determinants of the therapeutic burden associated with PC and its management.

scholarly journals Celebrating the 80th anniversary of hormone ablation for prostate cancer

2021 ◽  
Author(s):  
Paramita M Ghosh ◽  
Amina Zoubeidi
Keyword(s):  
Prostate Cancer ◽  
Drug Application ◽  
Parp Inhibitors ◽  
80Th Anniversary ◽  
Androgen Ablation ◽  
Androgen Withdrawal ◽  
Hormone Ablation ◽  
Anniversary Issue ◽  
History Of ◽  
Prostatic Atrophy

In this special issue of Endocrine-Related Cancer, we are celebrating the 80th anniversary of hormone ablation as treatment for metastatic prostate cancer. Our understanding has evolved from the observation that androgen withdrawal, either surgical or pharmacological, resulted in prostatic atrophy in animal models, to its application in patients, to investigation of the mysterious way in which prostate cancer escapes androgen dependence. We are now in an era of novel AR pathway inhibitors, combination of androgen ablation with chemotherapy, PARP inhibitors, immunotherapies, guided radiotherapy, and novel drug application based upon genetic testing of individual tumors. In this Anniversary Issue, we bring together a collection of eight reviews that cover not only the history of 80 years of progress after the initial identification of androgen ablation as an effective treatment of prostate cancer, but subsequent improvements in the understanding of the biology of the disease, development of novel treatment paradigms, resistance to those treatments and disease progression following that resistance.

scholarly journals Titration of Androgen Signaling: How Basic Studies Have Informed Clinical Trials Using High-Dose Testosterone Therapy in Castrate-Resistant Prostate Cancer

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 884
Author(s):  
Steven K. Nordeen ◽  
Lih-Jen Su ◽  
Gregory A. Osborne ◽  
Perry M. Hayman ◽  
David J. Orlicky ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Dose ◽  
Castration Resistant Prostate Cancer ◽  
Androgen Ablation ◽  
Clinical Observations ◽  
Clinical Benefits ◽  
Castrate Resistant Prostate Cancer ◽  
Prostate Cancers ◽  
Castrate Resistant ◽  
Basic Studies

Since the Nobel Prize-winning work of Huggins, androgen ablation has been a mainstay for treatment of recurrent prostate cancer. While initially effective for most patients, prostate cancers inevitably develop the ability to survive, grow, and metastasize further, despite ongoing androgen suppression. Here, we briefly review key preclinical studies over decades and include illustrative examples from our own laboratories that suggest prostate cancer cells titrate androgen signaling to optimize growth. Such laboratory-based studies argue that adaptations that allow growth in a low-androgen environment render prostate cancer sensitive to restoration of androgens, especially at supraphysiologic doses. Based on preclinical data as well as clinical observations, trials employing high-dose testosterone (HDT) therapy have now been conducted. These trials suggest a clinical benefit in cancer response and quality of life in a subset of castration-resistant prostate cancer patients. Laboratory studies also suggest that HDT may yet be optimized further to improve efficacy or durability of response. However, laboratory observations suggest that the cancer will inevitably adapt to HDT, and, as with prior androgen deprivation, disease progression follows. Nonetheless, the adaptations made to render tumors resistant to hormonal manipulations may reveal vulnerabilities that can be exploited to prolong survival and provide other clinical benefits.

scholarly journals Targeting androgen receptor signaling: a historical perspective

2021 ◽  
Author(s):  
Alastair H Davies ◽  
Amina Zoubeidi
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Historical Perspective ◽  
Death Sentence ◽  
Advanced Stage ◽  
Cancer Disease ◽  
Androgen Receptor Signaling ◽  
Androgen Ablation ◽  
First Case ◽  
Prostate Cancer Therapy

The first case of prostate cancer was identified by histological examination by J. Adams, a surgeon at The London Hospital, in 1853. In his report, Adams noted that the condition was “a very rare disease”. Now, over 150 years later, with increased life expectancy and screening, prostate cancer has become one of the most common cancers in men. In the United Sates alone, nearly 200,000 men are diagnosed with prostate cancer annually and about 33,000 succumb to their disease. Fifty years ago, men were typically diagnosed with prostate cancer in their seventies with disease that had metastasized to the bone and/or soft tissue. Diagnosis at such an advanced stage was a death sentence, with patients dying within two years. The pioneering work of Charles Huggins in the 1940s found that metastatic prostate cancer responds to androgen deprivation therapy (ADT), ushering in the rational use of hormone therapies that have irrevocably changed the course of prostate cancer disease management. Medical castration was the first effective systemic targeted therapy for any cancer and, to this day, androgen ablation remains the mainstay of prostate cancer therapy.

Long-Term Androgen Ablation and Docetaxel Up-Regulate Phosphorylated Akt in Castration Resistant Prostate Cancer

2011 ◽  
Vol 185 (6) ◽  
pp. 2376-2381 ◽  
Author(s):  
Takeo Kosaka ◽  
Akira Miyajima ◽  
Suguru Shirotake ◽  
Eriko Suzuki ◽  
Eiji Kikuchi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Androgen Ablation ◽  
Castration Resistant ◽  
Phosphorylated Akt
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