Prostate cancer remains an intractable threat to the lives of men worldwide.Although deaths from prostate cancer(PCa)in the United States have declined in recent years,in other parts of the world Pca mortality is incr...Prostate cancer remains an intractable threat to the lives of men worldwide.Although deaths from prostate cancer(PCa)in the United States have declined in recent years,in other parts of the world Pca mortality is increasing.The introduction of 2nd generation antiandrogen receptor agents into the therapeutic armamentarium for metastatic castrationresistant prostate cancer(mCRPC)has resulted in modestly increased survival advantages as demonstrated by initial clinical trials.However,analysis of the molecular pathways affected by these agents may lead to new insight into mechanisms of resistance that drive mCRPC,including proliferation and survival signaling pathways that are derepressed by maximum repression of androgen signaling.Combination therapies that involve anti-AR signaling agents together with agents that target these pathways establish a paradigm for the development of more effective treatment of mCRPC.In this review,we briefly summarize the current clinical trial literature with regard to novel anti-AR signaling agents such as abiraterone acetate and enzalutamide.We discuss observational data that point to mechanisms of resistance that emerged from these studies.We further present and discuss recent experimental studies that address the mechanisms of resistance to these treatments.Finally,we discuss novel and rational therapeutic approaches,including combination therapy,for patients with mCRPC.展开更多
Androgens play an important role in prostate cancer development and progression.Androgen action is mediated through the androgen receptor(AR),a ligand-dependent DNA-binding transcription factor.AR is arguably the most...Androgens play an important role in prostate cancer development and progression.Androgen action is mediated through the androgen receptor(AR),a ligand-dependent DNA-binding transcription factor.AR is arguably the most important target for prostate cancer treatment.Current USA Food and Drug Administration(FDA)-approved AR inhibitors target the ligand-binding domain(LBD)and have exhibited efficacy in prostate cancer patients,particularly when used in combination with androgen deprivation therapy.Unfortunately,patients treated with the currently approved AR-targeting agents develop resistance and relapse with castration-resistant prostate cancer(CRPC).The major mechanism leading to CRPC involves reactivation of AR signaling mainly through AR gene amplification,mutation,and/or splice variants.To effectively inhibit the reactivated AR signaling,new approaches to target AR are being actively explored.These new approaches include novel small molecule inhibitors targeting various domains of AR and agents that can degrade AR.The present review provides a summary of the existing FDA-approved AR antagonists and the current development of some of the AR targeting agents.展开更多
以高压汞灯和太阳光为光源,研究乙烯菌核利在重蒸水、自来水、湖水及pH缓冲液中的光解动力学。高压汞灯下,乙烯菌核利在重蒸水中的光解半衰期约为28 m in,而在太阳光下为3.86 h。自来水和湖水中溶解性物质对乙烯菌核利在高压汞灯下的光...以高压汞灯和太阳光为光源,研究乙烯菌核利在重蒸水、自来水、湖水及pH缓冲液中的光解动力学。高压汞灯下,乙烯菌核利在重蒸水中的光解半衰期约为28 m in,而在太阳光下为3.86 h。自来水和湖水中溶解性物质对乙烯菌核利在高压汞灯下的光解动力学仅有微弱的淬灭效应,但在太阳光下表现出显著的敏化效应,照光3 h的敏化效率分别为138%和126%。2种光源下,pH 5.0和pH 7.0缓冲液对乙烯菌核利的光解均表现为光淬灭效应,高压汞灯照光60 m in的淬灭效率分别为69%和57%,太阳光照光7 h的淬灭效率分别为77%和33%;pH 9.0缓冲液则表现出显著的敏化效应,高压汞灯照光20 m in的敏化效率为58%,而太阳光照光1 h的敏化效率则达到了415%。展开更多
Androgens play a prominent role in the development, maintenance and progression of prostate cancer. The introduction of androgen deprivation therapies into the treatment paradigm for prostate cancer patients has resul...Androgens play a prominent role in the development, maintenance and progression of prostate cancer. The introduction of androgen deprivation therapies into the treatment paradigm for prostate cancer patients has resulted in a wide variety of benefits ranging from a survival advantage for those with clinically localized or locally advanced disease, to improvements in symptom control for patients with advanced disease. Controversies remain, however, surrounding the optimal timing, duration and schedule of these hormonal approaches. Newer hormonal manipulations such as abiraterone acetate have also been investigated and will broaden treatment options for men with prostate cancer, This review highlights the various androgen-directed treatment options available to men with prostate cancer, their specific indications and the evidence supporting each approach, as well as patterns of use of hormonal therapies.展开更多
Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology to promote cancer research and accelerate collaborations. In this article, ...Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology to promote cancer research and accelerate collaborations. In this article, 10 questions are presented as followed. Question 76. How to develop effective therapeutics for cancer cachexia? Question 77.How can we develop preclinical animal models to recapitulate clinical situations of cancer patients for more effective anti-cancer drug development? Question 78. How can we develop novel effective therapeutics for pancreatic cancer and hepatocellular carcinoma? Question 79. What are the true beneficial mechanisms of antiangiogenic therapy in cancer patients? Question 80. How to approach the complex mechanisms of interplay among various cellular and molecular components in the tumor microenvironment? Question 81. Can tissue oxygenation improve the efficacy of conventional chemotherapy on cancer? Question 82. Can tissue oxygenation improve the efficacy of radiotherapy on digestive system tumors including liver cancer? Question 83. Can we integrate metabolic priming into multimodal management of liver cancer? Question 84. Has the limit of anti-androgen strategy in prostate cancer treatment been reached by the new generation of anti-androgen drugs? Question 85. Can we identify individuals with early-stage cancers via analyzing their clinical and non-clinical information collected from social media, shopping history, and clinical, pathological, and molecular traces?展开更多
基金supported in part by the National Institutes of Health through MD Anderson’s Cancer Center Support Grant,5 P30 CA16672the Department of Epidemiology,Second Military Medical University,Shanghai,China.
文摘Prostate cancer remains an intractable threat to the lives of men worldwide.Although deaths from prostate cancer(PCa)in the United States have declined in recent years,in other parts of the world Pca mortality is increasing.The introduction of 2nd generation antiandrogen receptor agents into the therapeutic armamentarium for metastatic castrationresistant prostate cancer(mCRPC)has resulted in modestly increased survival advantages as demonstrated by initial clinical trials.However,analysis of the molecular pathways affected by these agents may lead to new insight into mechanisms of resistance that drive mCRPC,including proliferation and survival signaling pathways that are derepressed by maximum repression of androgen signaling.Combination therapies that involve anti-AR signaling agents together with agents that target these pathways establish a paradigm for the development of more effective treatment of mCRPC.In this review,we briefly summarize the current clinical trial literature with regard to novel anti-AR signaling agents such as abiraterone acetate and enzalutamide.We discuss observational data that point to mechanisms of resistance that emerged from these studies.We further present and discuss recent experimental studies that address the mechanisms of resistance to these treatments.Finally,we discuss novel and rational therapeutic approaches,including combination therapy,for patients with mCRPC.
基金supported in part by DOD Idea Development Award(HT9425-23-1-0295)NIH grants(R01 CA265897 and R21 CA280467)by the Department of Urology,University of Pittsburgh School of Medicine,Pittsburgh,PA,USA。
文摘Androgens play an important role in prostate cancer development and progression.Androgen action is mediated through the androgen receptor(AR),a ligand-dependent DNA-binding transcription factor.AR is arguably the most important target for prostate cancer treatment.Current USA Food and Drug Administration(FDA)-approved AR inhibitors target the ligand-binding domain(LBD)and have exhibited efficacy in prostate cancer patients,particularly when used in combination with androgen deprivation therapy.Unfortunately,patients treated with the currently approved AR-targeting agents develop resistance and relapse with castration-resistant prostate cancer(CRPC).The major mechanism leading to CRPC involves reactivation of AR signaling mainly through AR gene amplification,mutation,and/or splice variants.To effectively inhibit the reactivated AR signaling,new approaches to target AR are being actively explored.These new approaches include novel small molecule inhibitors targeting various domains of AR and agents that can degrade AR.The present review provides a summary of the existing FDA-approved AR antagonists and the current development of some of the AR targeting agents.
文摘以高压汞灯和太阳光为光源,研究乙烯菌核利在重蒸水、自来水、湖水及pH缓冲液中的光解动力学。高压汞灯下,乙烯菌核利在重蒸水中的光解半衰期约为28 m in,而在太阳光下为3.86 h。自来水和湖水中溶解性物质对乙烯菌核利在高压汞灯下的光解动力学仅有微弱的淬灭效应,但在太阳光下表现出显著的敏化效应,照光3 h的敏化效率分别为138%和126%。2种光源下,pH 5.0和pH 7.0缓冲液对乙烯菌核利的光解均表现为光淬灭效应,高压汞灯照光60 m in的淬灭效率分别为69%和57%,太阳光照光7 h的淬灭效率分别为77%和33%;pH 9.0缓冲液则表现出显著的敏化效应,高压汞灯照光20 m in的敏化效率为58%,而太阳光照光1 h的敏化效率则达到了415%。
文摘Androgens play a prominent role in the development, maintenance and progression of prostate cancer. The introduction of androgen deprivation therapies into the treatment paradigm for prostate cancer patients has resulted in a wide variety of benefits ranging from a survival advantage for those with clinically localized or locally advanced disease, to improvements in symptom control for patients with advanced disease. Controversies remain, however, surrounding the optimal timing, duration and schedule of these hormonal approaches. Newer hormonal manipulations such as abiraterone acetate have also been investigated and will broaden treatment options for men with prostate cancer, This review highlights the various androgen-directed treatment options available to men with prostate cancer, their specific indications and the evidence supporting each approach, as well as patterns of use of hormonal therapies.
文摘Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology to promote cancer research and accelerate collaborations. In this article, 10 questions are presented as followed. Question 76. How to develop effective therapeutics for cancer cachexia? Question 77.How can we develop preclinical animal models to recapitulate clinical situations of cancer patients for more effective anti-cancer drug development? Question 78. How can we develop novel effective therapeutics for pancreatic cancer and hepatocellular carcinoma? Question 79. What are the true beneficial mechanisms of antiangiogenic therapy in cancer patients? Question 80. How to approach the complex mechanisms of interplay among various cellular and molecular components in the tumor microenvironment? Question 81. Can tissue oxygenation improve the efficacy of conventional chemotherapy on cancer? Question 82. Can tissue oxygenation improve the efficacy of radiotherapy on digestive system tumors including liver cancer? Question 83. Can we integrate metabolic priming into multimodal management of liver cancer? Question 84. Has the limit of anti-androgen strategy in prostate cancer treatment been reached by the new generation of anti-androgen drugs? Question 85. Can we identify individuals with early-stage cancers via analyzing their clinical and non-clinical information collected from social media, shopping history, and clinical, pathological, and molecular traces?
