cabazitaxel with enzalutamide for PCa

Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men. Localised PCa can be treated effectively, but most patients relapse/progress to more aggressive disease. One possible mechanism underlying this progression is alternative splicing of the androgen receptor, with AR variant 7(ARV7) considered to play a major role. Using viability assays, we confirmed that ARV7-positive PCa cells were less sensitive to treatment with cabazitaxel and an anti-androgen-enzalutamide. Also, using live-holographic imaging, we showed that PCa cells with ARV7 exhibited an increased rate of cell division, proliferation, and motility, which could potentially contribute to a more aggressive phenotype...

INTRODUCTION: Relugolix is the first oral gonadotrophin-releasing hormone (GnRH) receptor antagonist. Based on the phase III HERO trial results, relugolix received Food and Drug Administration approval for adult patients with advanced prostate cancer (PCa). AREAS COVERED: We provide an overview of the preclinical and clinical development of relugolix and its role in the current treatment landscape of PCa. EXPERT OPINION: Relugolix leads to rapid inhibition of testicular production of testosterone and its rapid recovery upon discontinuation...

OBJECTIVE: Prostate cancer (PCa) is the second most common solid tumor in men and the fifth leading cause of cancer-related death. In advanced stage, palliative treatments are used instead of curative therapies. Therefore, finding predictive indicators seems crucial. Patients with castration-resistant prostate cancer (CRPC) that received Dx chemotherapy have been retrospectively reviewed. The aim of this study was to investigate whether docetaxel (Dx)-free interval could have a predictive value for PCa and influence other sequential therapies...

Organoid-based studies have revolutionized in vitro preclinical research and hold great promise for the cancer research field, including prostate cancer (PCa). However, experimental variability in organoid drug testing complicates reproducibility. For example, we observed PCa organoids to be less affected by cabazitaxel, abiraterone and enzalutamide as compared to corresponding single cells prior to organoid assembly. We hypothesized that three-dimensional (3D) organoid organization and the use of various 3D scaffolds impact treatment efficacy...

BACKGROUND: The androgen receptor (AR) pathway is a key driver of neoplastic behaviour in the different stages of metastatic prostate cancer (mPCa). Targeting the AR therefore remains the cornerstone for mPCa treatment. We have previously reported that activation of AR signalling affects taxane chemo-sensitivity in preclinical models of castration resistant PCa (CRPC). Here, we explored the anti-tumour efficacy of the AR targeted inhibitor enzalutamide combined with cabazitaxel. METHODS: We used the AR positive CRPC model PC346C-DCC-K to assess the in vitro and in vivo activity of combining enzalutamide with cabazitaxel...

Prostate cancer (PCa) is the fifth cause of tumor-related deaths in man worldwide. Despite the considerable improvement in the clinical management of PCa, several limitations emerged both in the screening for early diagnosis and in the medical treatment. The use of prostate-specific antigen (PSA)-based screening resulted in patients' overtreatment and the standard therapy of patients suffering from locally advanced/metastatic tumors (e.g., radical prostatectomy, radiotherapy, and androgen deprivation therapy) showed time-limited efficacy with patients undergoing progression toward the lethal metastatic castration-resistant PCa (mCRPC)...

Efficacy and mechanism of action of marine alkaloid 3,10-dibromofascaplysin (DBF) were investigated in human prostate cancer (PCa) cells harboring different levels of drug resistance. Anticancer activity was observed across all cell lines examined without signs of cross-resistance to androgen receptor targeting agents (ARTA) or taxane based chemotherapy. Kinome analysis followed by functional investigation identified JNK1/2 to be one of the molecular targets of DBF in 22Rv1 cells. In contrast, no activation of p38 and ERK1/2 MAPKs was observed...

OBJECTIVE: Review the latest evidence on urologic oncology on kidney, bladder and prostate tumors. METHODS: Abstracts on kidney, bladder and prostate cancer presented at the 2019 congresses (EAU, AUA, ASCO and ESMO) and the publications with the greatest impact in this period, with the highest evaluation by the OncoForum committee, are reviewed. RESULTS: In patients with metastatic kidney cancer, regimens including immunotherapy (nivolumab + ipilimumab, pembrolizumab) have been shown to be superior to sunitinib in terms of survival...

Introduction : Prostate cancer (PCa) is one of the most common adult malignancies worldwide, and a major leading cause of cancer-related death in men in Western societies. In the last years, the prognosis of advanced PCa patients has been impressively improved thanks to the development of different therapeutic agents, including taxanes (docetaxel and cabazitaxel), second-generation anti-hormonal agents (abiraterone and enzalutamide), and the radiopharmaceutical Radium-223. However, great efforts are still needed to properly select the most appropriate treatment for each single patient...

The management of metastatic prostate cancer (mPCa) has changed over the past ten years. Several new drugs have been approved with significant overall survival benefits in metastatic castration resistant prostate cancer (PCa) including chemotherapy (docetaxel, cabazitaxel), new hormonal therapies (abiraterone, enzalutamide), Radium-223 and immunotherapy. The addition of docetaxel to androgen deprivation therapy (ADT) versus ADT alone in the castration sensitive metastatic setting has gained significant overall survival benefit particularly for high volume disease...

INTRODUCTION: Since just after the year 2000 in Quebec, the management of metastatic castration-resistant prostate cancer (mcrpc) has evolved considerably, with the inclusion of docetaxel-based chemotherapy, bone-targeted therapies (zoledronic acid and denosumab), and more recently, abiraterone, enzalutamide, and cabazitaxel for docetaxel-refractory patients. In the present study, we aimed to analyze contemporary mcrpc management patterns and therapy utilization trends in Quebec. METHODS: The study cohort consisted of patients dying of prostate cancer (pca) between January 2001 and December 2013, selected from Quebec public health care insurance databases...

OBJECTIVE: To present a summary of the 2016 version of the European Association of Urology (EAU) - European Society for Radiotherapy & Oncology (ESTRO) - International Society of Geriatric Oncology (SIOG) Guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (CRPC). EVIDENCE ACQUISITION: The working panel performed a literature review of the new data (2013-2015). The guidelines were updated, and the levels of evidence and/or grades of recommendation were added based on a systematic review of the literature...

OBJECTIVE: To present a summary of the 2013 version of the European Association of Urology (EAU) guidelines on the treatment of advanced, relapsing, and castration-resistant prostate cancer (CRPC). EVIDENCE ACQUISITION: The working panel performed a literature review of the new data (2011-2013). The guidelines were updated, and levels of evidence and/or grades of recommendation were added to the text based on a systematic review of the literature that included a search of online databases and bibliographic reviews...

Prostate cancer (PCa) is the most common malignancy, and the third leading cancer-related cause of death among men of the Western world. Upon PCa progression into metastatic disease, androgen deprivation therapy is applied as the first-line treatment, and has been shown to be effective in most patients, leading to a decrease in serum prostate-specific antigen and relief of disease-related symptoms. However, advanced PCa almost inevitably progresses to a castration-resistant state, and is currently regarded as incurable...