Interleukin-6(IL-6)is a pleiotropic cytokine involved in prostate regulation and in prostate cancer(PC)development/progression.IL-6 acts as a paracrine and autocrine growth stimulator in benign and tumor prostate cell...Interleukin-6(IL-6)is a pleiotropic cytokine involved in prostate regulation and in prostate cancer(PC)development/progression.IL-6 acts as a paracrine and autocrine growth stimulator in benign and tumor prostate cells.The levels of IL-6 and respective receptors are increased during prostate carcinogenesis and tumor progression.Several studies reported that increased serum and plasma IL-6 and soluble interleukin-6 receptor levels are associated with aggressiveness of the disease and are associated with a poor prognosis in PC patients.In PC treatment,patients diagnosed with advanced stages are frequently submitted to hormonal castration,although most patients will eventually fail this therapy and die from recurrent castration-resistant prostate cancer(CRPC).Therefore,it is important to understand the mechanisms involved in CRPC.Several pathways have been proposed to be involved in CRPC development,and their understanding will improve the way to more effective therapies.In fact,the prostate is known to be dependent,not exclusively,on androgens,but also on growth factors and cytokines.The signaling pathway mediated by IL-6 may be an alternative pathway in the CRPC phenotype acquisition and cancer progression,under androgen deprivation conditions.The principal goal of this review is to evaluate the role of IL-6 pathway signaling in human PC development and progression and discuss the interaction of this pathway with the androgen recepto pathway.Furthermore,we intend to evaluate the inclusion of IL-6 and its receptor levels as a putative new class of tumor biomarkers.The IL-6/IL-6R signaling pathway may be included as a putative molecular marker for aggressiveness in PC and it may be able to maintain tumor growth through the AR pathway under androgen-deprivation conditions.The importance of the IL-6/IL-6R pathway in regulation of PC cells makes it a good candidate for targeted therapy.展开更多
AIdo-keto reductase family 1 member C3 has recently been regarded as a potential therapeutic target in castrate-resistant prostate cancer. Herein, we investigated whether berberine delayed the progression of castrate-...AIdo-keto reductase family 1 member C3 has recently been regarded as a potential therapeutic target in castrate-resistant prostate cancer. Herein, we investigated whether berberine delayed the progression of castrate-resistant prostate cancer by reducing androgen synthesis through the inhibition of Aldo-keto reductase family 1 member C3. Cell viability and cellular testosterone content were measured in prostate cancer cells. Aido-keto reductase family 1 member C3 mRNA and protein level were detected by RT-PCR and Western bolt analyses, respectively. Computer analysis with AutoDock Tools explored the molecular interaction of berberine with Aldo-keto reductase family 1 member C3. We found that berberine inhibited 22Rvl cells proliferation and decreased cellular testosterone formation in a dose-dependent manner. Berberine inhibited Aldo-keto reductase family I member C3 enzyme activity, rather than influenced mRNA and protein expressions. Molecular docking study demonstrated that berberine could enter the active center of Aldo-keto reductase family 1 member C3 and form π-π interaction with the amino-acid residue Phe306 and Phe311. In conclusion, the structural interaction of berberine with Aldo-keto reductase family 1 member C3 is attributed to the suppression of Aldo-keto reductase family I member C3 enzyme activity and the inhibition of 22Rvl prostate cancer cell growth by decreasing the intfacellular androgen synthesis. Our result provides the experimental basis for the design, research, and development of AKRlC3 inhibitors using berberine as the lead compound.展开更多
This study aims to evaluate the potential value of patient characteristics in predicting overall survival （OS） in patients with metastatic castration-resistant prostate cancer （mCRPC） treated with docetaxel-based ...This study aims to evaluate the potential value of patient characteristics in predicting overall survival （OS） in patients with metastatic castration-resistant prostate cancer （mCRPC） treated with docetaxel-based thermotherapy. A total of 115 patients with mCRPC undergoing a docetaxel q3w regimen were enrolled in this study. A survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards models were used to evaluate the prognostic value of all covariates for OS. OS was also analysed after stratifying patients according to the results of multivariate analysis. The median OS for the entire cohort was 17.0 months. The multivariate analysis showed that the prostate-specific antigen doubling time （PSADT）, baseline haemoglobin （Hb） concentration, alkaline phosphatase （ALP） concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS. According to the presence of PSADT 〈46.3 days and baseline ALP/〉 110 IU 1-1, all patients were divided into three risk groups： low-risk group （no risk factors）, intermediate-risk group （one risk factor） and high-risk group （two risk factors）. Median OSs for patients in low-, intermediate- and high-risk groups were 28.0 months （95% Ch 23.8-32.2）, 21.0 months （95% Ch 18.9-23.1） and 11.0 months （95% Ch 7.6-14.4）, respectively （P〈O.O01）. In conclusion, PSADT, baseline Hb concentration, ALP concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS in Chinese patients with mCRPC treated with docetaxel. PSADT combined with the baseline ALP concentration could be a useful risk stratification parameter for evaluating survival outcomes.展开更多
Owing to incurable castration-resistant prostate cancer(CRPC)ultimately developing after treating with androgen deprivation therapy(ADT),it is vital to devise new therapeutic strategies to treat CRPC.Treatments that t...Owing to incurable castration-resistant prostate cancer(CRPC)ultimately developing after treating with androgen deprivation therapy(ADT),it is vital to devise new therapeutic strategies to treat CRPC.Treatments that target programmed cell death protein 1(PD-1)and programmed death ligand-1(PD-L1)have been approved for human cancers with clinical benefit.However,many patients,especially prostate cancer,fail to respond to anti-PD-1/PD-L1 treatment,so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy.In the present study,analyzing the data from our prostate cancer tissue microarray,we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L(Hn RNP L).Hence,we further investigated the potential role of Hn RNP L on the PD-L1 expression,the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC.Indeed,Hn RNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo,on the contrary,Hn RNP L overexpression led to the opposite effect in CRPC cells.In addition,consistent with the previous study,we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death,and Hn RNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells.Furthermore,Hn RNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8^(+)T cells and synergized with anti-PD-1 therapy in CRPC tumors.This study provided biological evidence that Hn RNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.展开更多
Availability of novel hormonal therapies as well as docetaxel and cabazitaxel treatment for metastatic castration-resistant prostate cancer （CRPC） has changed the outlook for this group of patients with improvements...Availability of novel hormonal therapies as well as docetaxel and cabazitaxel treatment for metastatic castration-resistant prostate cancer （CRPC） has changed the outlook for this group of patients with improvements in progression-free survival and overall survival. Physicians often diagnose the progression of prostate cancer using serum prostate-specific antigen （PSA）. However, serum PSA is not always correlated with the clinical status in CRPC. To evaluate the PSA dynamics with greater precision, understanding of the control of PSA and of the mechanisms of development of CRPC is needed. Moreover, it is necessary to use new hormonal therapies with an appropriate timing to optimally improve the prognosis and the QOL of the patients. In the present review, we ascertain the PSA dynamics and the mechanisms of the development of CRPC to assist in optimal utilization of the new treatments for mCRPC.展开更多
Despite its good initial response and significant survival benefit in patients with castrationresistant prostate cancer(CRPC), taxane therapy inevitably encounters drug resistance in all patients.Deep understandings o...Despite its good initial response and significant survival benefit in patients with castrationresistant prostate cancer(CRPC), taxane therapy inevitably encounters drug resistance in all patients.Deep understandings of taxane resistant mechanisms can significantly facilitate the development of new therapeutic strategies to overcome taxane resistance and improve CRPC patient survival. Multiple pathways of resistance have been identified as potentially crucial areas of intervention. First, taxane resistant tumor cells typically have mutated microtubule binding sites, varying tubulin isotype expression,and upregulation of efflux transporters. These mechanisms contribute to reducing binding affinity and availability of taxanes. Second, taxane resistant tumors have increased stem cell like characteristics,indicating higher potential for further mutation in response to therapy. Third, the androgen receptor pathway is instrumental in the proliferation of CRPC and multiple hypotheses leading to this pathway reactivation have been reported. The connection of this pathway to the AKT pathway has received significant attention due to the upregulation of phosphorylated AKT in CRPC. This review highlights recent advances in elucidating taxane resistant mechanisms and summarizes potential therapeutic strategies for improved treatment of CRPC.展开更多
Lacking a precise targeting strategy,castration-resistant prostate cancer(CRPC)is still hard to be treat effectively.Exploring treatment options that can accurately target CPRC is an important issue with urgent need.I...Lacking a precise targeting strategy,castration-resistant prostate cancer(CRPC)is still hard to be treat effectively.Exploring treatment options that can accurately target CPRC is an important issue with urgent need.In this study,a novel nanotechnologybased strategy had been developed for the precise target treatment of CRPC.By combining microwaves and photothermal therapy(PTT),this nanoplatform,cmHSP70-PL-AuNC-DOX,targets tumor tissues with outstanding precision and achieves better anti-tumor activity by simultaneously eliciting photothermal and chemotherapeutic effects.From nanotechnology,cmHSP70-modified and thermo-sensitive liposome-coated AuNC-DOX were prepared and used for CRPC-targeted photothermal ablation and chemotherapy.Doxorubicin(DOX)was selected as the chemotherapeutic agent for cytotoxicity.In terms of the curative scheme,prostate tissues were firstly pre-treated with microwaves to induce the expression of heat shock protein 70(HSP70)and its migration to the cell membrane,which was then targeted by HSP70 antibody(cmHSP70)coated on the nanoparticles to achieve accurate drug delivery.The nanoplatform then achieved precise ablation and controlled release of DOX under external near-infrared(NIR)irradiation.Through the implementation,the targeting,cell killing,and safety of this therapeutical strategy had been verified in vivo and in vitro.This work establishes an accurate,controllable,efficient,non-invasive,and safe treatment platform for targeting CRPC,provides a rational design for CRPC’s PTT,and offers new prospects for nanomedicines with great precision.展开更多
Prostate cancer (PCa) is the most common cause of malignancy in males and the third leading cause of cancer mortality in the United States. The standard care for primary PCa with local invasive disease mainly is surge...Prostate cancer (PCa) is the most common cause of malignancy in males and the third leading cause of cancer mortality in the United States. The standard care for primary PCa with local invasive disease mainly is surgery and radiation. For patients with distant metastases, androgen deprivation therapy (ADT) is a gold standard. Regardless of a favorable outcome of ADT, patients inevitably relapse to an end-stage castration-resistant prostate cancer (CRPC) leading to mortality. Therefore, revealing the mechanism and identifying cellular components driving aggressive PCa is critical for prognosis and therapeutic intervention. Cancer stem cell (CSC) phenotypes characterized as poor differentiation, cancer initiation with self-renewal capabilities, and therapeutic resistance are proposed to contribute to the onset of CRPC. In this review, we discuss the role of CSC in CRPC with the evidence of CSC phenotypes and the possible underlying mechanisms.展开更多
Purpose: The purpose of this paper is to discuss the most important facts about prostate cancer, its treatments and efficacy, the type of prostate cancer that does not improve with hormonal therapy (Castration-Resista...Purpose: The purpose of this paper is to discuss the most important facts about prostate cancer, its treatments and efficacy, the type of prostate cancer that does not improve with hormonal therapy (Castration-Resistant Prostate Cancer-CRPC), and the recently approved Radium-223 dichloride targeted therapy for CRPC that has metastasized to bones. Prostate cancer is the third most common malignancy diagnosed worldwide and the most common malignant disease in men. Also, the incidence of prostate cancer varies between regions. So it’s important to have a proper understanding of all above points to prevent the further development and spread of cancer and improve the cure rate. Design: The paper begins by discussing what prostate cancer is, the risk factors, clinical manifestations, and the treatments for prostate cancer. It covers the clinical manifestations, pathology, screening (cancer biomarker Prostate Specific Antigen, Digital Rectal Examination—DRE, prostate biopsy, and imaging) and treatments for prostate cancer. The paper then delves into the main treatment methods for prostate cancer, including how Castration-Resistant Prostate Cancer (CRPC) differs from normal prostate cancer after hormone suppression therapy. Additionally, it discusses the effectiveness of the recently introduced Radium-223 dichloride injection as a radiation-targeted therapy for treating CRPC that has metastasized to bones. This section covers the properties of radium-223 dichloride injection, its pharmacokinetics, pharmacodynamics, absorption and volume of distribution, half-life, metabolism, route of elimination, clearance, toxicity, adverse effects, and mechanism of action at the tumor site. It also discusses preclinical studies related to radium-223 dichloride injection and its effectiveness in treating CRPC patients with bone metastasis. Conclusion: Prostate cancer is a common cancer that can be treated with surgery or hormonal therapy. However, if the cancer progresses despite hormonal therapy, Radium-223 dichloride injection ca展开更多
文摘Interleukin-6(IL-6)is a pleiotropic cytokine involved in prostate regulation and in prostate cancer(PC)development/progression.IL-6 acts as a paracrine and autocrine growth stimulator in benign and tumor prostate cells.The levels of IL-6 and respective receptors are increased during prostate carcinogenesis and tumor progression.Several studies reported that increased serum and plasma IL-6 and soluble interleukin-6 receptor levels are associated with aggressiveness of the disease and are associated with a poor prognosis in PC patients.In PC treatment,patients diagnosed with advanced stages are frequently submitted to hormonal castration,although most patients will eventually fail this therapy and die from recurrent castration-resistant prostate cancer(CRPC).Therefore,it is important to understand the mechanisms involved in CRPC.Several pathways have been proposed to be involved in CRPC development,and their understanding will improve the way to more effective therapies.In fact,the prostate is known to be dependent,not exclusively,on androgens,but also on growth factors and cytokines.The signaling pathway mediated by IL-6 may be an alternative pathway in the CRPC phenotype acquisition and cancer progression,under androgen deprivation conditions.The principal goal of this review is to evaluate the role of IL-6 pathway signaling in human PC development and progression and discuss the interaction of this pathway with the androgen recepto pathway.Furthermore,we intend to evaluate the inclusion of IL-6 and its receptor levels as a putative new class of tumor biomarkers.The IL-6/IL-6R signaling pathway may be included as a putative molecular marker for aggressiveness in PC and it may be able to maintain tumor growth through the AR pathway under androgen-deprivation conditions.The importance of the IL-6/IL-6R pathway in regulation of PC cells makes it a good candidate for targeted therapy.
基金This work was supported by grants from the National Natural Science Foundation of China （81302206 and 81560422）, the Development and Reform Commission of Jilin Province （2013C026-2）, and the Young Scholars Program of Norman Bethune Health Science Center of Jilin University （2013201012）, the Health and Family Planning Commission of Jiangxi Province （20143207） and the Natural Science Foundation of Jiangxi Province of China （20151BAB205016 and 20132BAB205008）.
文摘AIdo-keto reductase family 1 member C3 has recently been regarded as a potential therapeutic target in castrate-resistant prostate cancer. Herein, we investigated whether berberine delayed the progression of castrate-resistant prostate cancer by reducing androgen synthesis through the inhibition of Aldo-keto reductase family 1 member C3. Cell viability and cellular testosterone content were measured in prostate cancer cells. Aido-keto reductase family 1 member C3 mRNA and protein level were detected by RT-PCR and Western bolt analyses, respectively. Computer analysis with AutoDock Tools explored the molecular interaction of berberine with Aldo-keto reductase family 1 member C3. We found that berberine inhibited 22Rvl cells proliferation and decreased cellular testosterone formation in a dose-dependent manner. Berberine inhibited Aldo-keto reductase family I member C3 enzyme activity, rather than influenced mRNA and protein expressions. Molecular docking study demonstrated that berberine could enter the active center of Aldo-keto reductase family 1 member C3 and form π-π interaction with the amino-acid residue Phe306 and Phe311. In conclusion, the structural interaction of berberine with Aldo-keto reductase family 1 member C3 is attributed to the suppression of Aldo-keto reductase family I member C3 enzyme activity and the inhibition of 22Rvl prostate cancer cell growth by decreasing the intfacellular androgen synthesis. Our result provides the experimental basis for the design, research, and development of AKRlC3 inhibitors using berberine as the lead compound.
文摘This study aims to evaluate the potential value of patient characteristics in predicting overall survival （OS） in patients with metastatic castration-resistant prostate cancer （mCRPC） treated with docetaxel-based thermotherapy. A total of 115 patients with mCRPC undergoing a docetaxel q3w regimen were enrolled in this study. A survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards models were used to evaluate the prognostic value of all covariates for OS. OS was also analysed after stratifying patients according to the results of multivariate analysis. The median OS for the entire cohort was 17.0 months. The multivariate analysis showed that the prostate-specific antigen doubling time （PSADT）, baseline haemoglobin （Hb） concentration, alkaline phosphatase （ALP） concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS. According to the presence of PSADT 〈46.3 days and baseline ALP/〉 110 IU 1-1, all patients were divided into three risk groups： low-risk group （no risk factors）, intermediate-risk group （one risk factor） and high-risk group （two risk factors）. Median OSs for patients in low-, intermediate- and high-risk groups were 28.0 months （95% Ch 23.8-32.2）, 21.0 months （95% Ch 18.9-23.1） and 11.0 months （95% Ch 7.6-14.4）, respectively （P〈O.O01）. In conclusion, PSADT, baseline Hb concentration, ALP concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS in Chinese patients with mCRPC treated with docetaxel. PSADT combined with the baseline ALP concentration could be a useful risk stratification parameter for evaluating survival outcomes.
基金supported by the National Natural Science Foundation of China(Grant No.81773277)Science and Technology Program of Guangzhou,China(Grant No.201803010014)+3 种基金Guangdong Basic and Applied Basic Research Foundation(Grant Nos.2020A1515110922 and 2019A1515110033,China)China Postdoctoral Science Foundation funded project(Grant Nos.2018M643126 and 2019M662865)Distinguished Young Talents in Higher Education Foundation of Guangdong Province(Grant No.2019KQNCX115,China)Achievement Cultivation and Clinical Transformation Application Cultivation Projects of the First Affiliated Hospital of Guangzhou Medical University(Grant No.ZH201908,China)。
文摘Owing to incurable castration-resistant prostate cancer(CRPC)ultimately developing after treating with androgen deprivation therapy(ADT),it is vital to devise new therapeutic strategies to treat CRPC.Treatments that target programmed cell death protein 1(PD-1)and programmed death ligand-1(PD-L1)have been approved for human cancers with clinical benefit.However,many patients,especially prostate cancer,fail to respond to anti-PD-1/PD-L1 treatment,so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy.In the present study,analyzing the data from our prostate cancer tissue microarray,we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L(Hn RNP L).Hence,we further investigated the potential role of Hn RNP L on the PD-L1 expression,the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC.Indeed,Hn RNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo,on the contrary,Hn RNP L overexpression led to the opposite effect in CRPC cells.In addition,consistent with the previous study,we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death,and Hn RNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells.Furthermore,Hn RNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8^(+)T cells and synergized with anti-PD-1 therapy in CRPC tumors.This study provided biological evidence that Hn RNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.
文摘Availability of novel hormonal therapies as well as docetaxel and cabazitaxel treatment for metastatic castration-resistant prostate cancer （CRPC） has changed the outlook for this group of patients with improvements in progression-free survival and overall survival. Physicians often diagnose the progression of prostate cancer using serum prostate-specific antigen （PSA）. However, serum PSA is not always correlated with the clinical status in CRPC. To evaluate the PSA dynamics with greater precision, understanding of the control of PSA and of the mechanisms of development of CRPC is needed. Moreover, it is necessary to use new hormonal therapies with an appropriate timing to optimally improve the prognosis and the QOL of the patients. In the present review, we ascertain the PSA dynamics and the mechanisms of the development of CRPC to assist in optimal utilization of the new treatments for mCRPC.
基金partially supported by NIH grants 1R01CA148706 and 1R01CA193609 to Wei Li
文摘Despite its good initial response and significant survival benefit in patients with castrationresistant prostate cancer(CRPC), taxane therapy inevitably encounters drug resistance in all patients.Deep understandings of taxane resistant mechanisms can significantly facilitate the development of new therapeutic strategies to overcome taxane resistance and improve CRPC patient survival. Multiple pathways of resistance have been identified as potentially crucial areas of intervention. First, taxane resistant tumor cells typically have mutated microtubule binding sites, varying tubulin isotype expression,and upregulation of efflux transporters. These mechanisms contribute to reducing binding affinity and availability of taxanes. Second, taxane resistant tumors have increased stem cell like characteristics,indicating higher potential for further mutation in response to therapy. Third, the androgen receptor pathway is instrumental in the proliferation of CRPC and multiple hypotheses leading to this pathway reactivation have been reported. The connection of this pathway to the AKT pathway has received significant attention due to the upregulation of phosphorylated AKT in CRPC. This review highlights recent advances in elucidating taxane resistant mechanisms and summarizes potential therapeutic strategies for improved treatment of CRPC.
基金This study was supported by the National Natural Science Foundation of China(Nos.82172679 and 82104405)Zhejiang Provincial Medicine and Health Science Foundation(No:2021KY010).
文摘Lacking a precise targeting strategy,castration-resistant prostate cancer(CRPC)is still hard to be treat effectively.Exploring treatment options that can accurately target CPRC is an important issue with urgent need.In this study,a novel nanotechnologybased strategy had been developed for the precise target treatment of CRPC.By combining microwaves and photothermal therapy(PTT),this nanoplatform,cmHSP70-PL-AuNC-DOX,targets tumor tissues with outstanding precision and achieves better anti-tumor activity by simultaneously eliciting photothermal and chemotherapeutic effects.From nanotechnology,cmHSP70-modified and thermo-sensitive liposome-coated AuNC-DOX were prepared and used for CRPC-targeted photothermal ablation and chemotherapy.Doxorubicin(DOX)was selected as the chemotherapeutic agent for cytotoxicity.In terms of the curative scheme,prostate tissues were firstly pre-treated with microwaves to induce the expression of heat shock protein 70(HSP70)and its migration to the cell membrane,which was then targeted by HSP70 antibody(cmHSP70)coated on the nanoparticles to achieve accurate drug delivery.The nanoplatform then achieved precise ablation and controlled release of DOX under external near-infrared(NIR)irradiation.Through the implementation,the targeting,cell killing,and safety of this therapeutical strategy had been verified in vivo and in vitro.This work establishes an accurate,controllable,efficient,non-invasive,and safe treatment platform for targeting CRPC,provides a rational design for CRPC’s PTT,and offers new prospects for nanomedicines with great precision.
文摘Prostate cancer (PCa) is the most common cause of malignancy in males and the third leading cause of cancer mortality in the United States. The standard care for primary PCa with local invasive disease mainly is surgery and radiation. For patients with distant metastases, androgen deprivation therapy (ADT) is a gold standard. Regardless of a favorable outcome of ADT, patients inevitably relapse to an end-stage castration-resistant prostate cancer (CRPC) leading to mortality. Therefore, revealing the mechanism and identifying cellular components driving aggressive PCa is critical for prognosis and therapeutic intervention. Cancer stem cell (CSC) phenotypes characterized as poor differentiation, cancer initiation with self-renewal capabilities, and therapeutic resistance are proposed to contribute to the onset of CRPC. In this review, we discuss the role of CSC in CRPC with the evidence of CSC phenotypes and the possible underlying mechanisms.
文摘Purpose: The purpose of this paper is to discuss the most important facts about prostate cancer, its treatments and efficacy, the type of prostate cancer that does not improve with hormonal therapy (Castration-Resistant Prostate Cancer-CRPC), and the recently approved Radium-223 dichloride targeted therapy for CRPC that has metastasized to bones. Prostate cancer is the third most common malignancy diagnosed worldwide and the most common malignant disease in men. Also, the incidence of prostate cancer varies between regions. So it’s important to have a proper understanding of all above points to prevent the further development and spread of cancer and improve the cure rate. Design: The paper begins by discussing what prostate cancer is, the risk factors, clinical manifestations, and the treatments for prostate cancer. It covers the clinical manifestations, pathology, screening (cancer biomarker Prostate Specific Antigen, Digital Rectal Examination—DRE, prostate biopsy, and imaging) and treatments for prostate cancer. The paper then delves into the main treatment methods for prostate cancer, including how Castration-Resistant Prostate Cancer (CRPC) differs from normal prostate cancer after hormone suppression therapy. Additionally, it discusses the effectiveness of the recently introduced Radium-223 dichloride injection as a radiation-targeted therapy for treating CRPC that has metastasized to bones. This section covers the properties of radium-223 dichloride injection, its pharmacokinetics, pharmacodynamics, absorption and volume of distribution, half-life, metabolism, route of elimination, clearance, toxicity, adverse effects, and mechanism of action at the tumor site. It also discusses preclinical studies related to radium-223 dichloride injection and its effectiveness in treating CRPC patients with bone metastasis. Conclusion: Prostate cancer is a common cancer that can be treated with surgery or hormonal therapy. However, if the cancer progresses despite hormonal therapy, Radium-223 dichloride injection ca
