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Current treatments and novel therapeutic targets for castration resistant prostate cancer with bone metastasis.

ABSTRACT: Prostate cancer is a leading cause of cancer death in men in developed countries. While early stage disease can often be cured, many patients eventually develop castration resistant prostate cancer (CRPC). The majority of CRPC patients have bone metastases, which cause significant morbidity and mortality. Although there is no cure for prostate cancer metastatic to bone, several bone-targeted agents have been approved to prevent skeletal-related events (SREs). Among them, bisphosphonates were the first class of drugs investigated for prevention of SREs. Denosumab is a recently approved agent that binds to the receptor activator of nuclear factor-?B ligand (RANKL) as a humanized monoclonal antibody. Both agents target prostate cancer skeletal metastasis through the inhibition of bone resorption. Alpharadin is the first radiopharmaceutical agent that has significant overall survival benefit. It has benefits in pain palliation and SREs as well. Another newly approved drug is Abiraterone acetate, which decreases circulating levels of testosterone by targeting an enzyme expressed in the testis and the adrenal, as well as in prostate cancer tissues. This review outlines the clinical and preclinical data supporting the use of these and new agents in development for CRPC with bone metastasis.

SUBMITTER: Wei J

PROVIDER: S-EPMC4219282 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Current treatments and novel therapeutic targets for castration resistant prostate cancer with bone metastasis.

Wei Juncheng J Wang Zhilin Z Makarov Danil D Li Xin X

American journal of clinical and experimental urology 20131225 1

Prostate cancer is a leading cause of cancer death in men in developed countries. While early stage disease can often be cured, many patients eventually develop castration resistant prostate cancer (CRPC). The majority of CRPC patients have bone metastases, which cause significant morbidity and mortality. Although there is no cure for prostate cancer metastatic to bone, several bone-targeted agents have been approved to prevent skeletal-related events (SREs). Among them, bisphosphonates were the ...[more]

PMID: 25374898

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Project description:Prostate carcinoma is a highly prevalent biologically and clinically diverse disease, generally associated with a consistent elevation of prostate-specific antigen levels. Castration-resistant prostate cancer represents a heterogeneous clinical setting that ranges from patients with an asymptomatic prostate-specific antigen elevation after hormone blockade failure and good performance status to patients with significant debilitating symptoms and rapidly progressive disease, leading to death. Nonmetastatic castration-resistant prostate cancer is a transient disease stage defined over specific criteria established within a sensitive time period. The majority of the patients with nonmetastatic castration-resistant prostate cancer will eventually develop metastatic lesions, associated with prostate cancer-specific morbidity and mortality. However, progression to metastatic disease is a heterogeneous process still not fully understood, with studies suggesting that younger age, high Gleason score (> 7), high prostate-specific antigen levels, reduced prostate-specific antigen doubling time (< 6 months), and a rapid alkaline phosphatase rise as potentially associated factors. Although the nonmetastatic castration-resistant prostate cancer treatment landscape has substantially evolved in recent years, the disease heterogeneity makes treatment decisions for this population challenging in the effort to achieve a balance between the risk of disease progression and the toxicity of new treatments in patients who often have associated comorbidities, yet are generally asymptomatic. The present article addresses the current main challenges in nonmetastatic castration-resistant prostate cancer management, including in diagnosis, owing to the development of new imaging modalities with a direct impact in disease detection, prognostic classification, as a result of the traditionally oversimplified definition of disease aggressiveness (mainly based on prostate-specific antigen doubling time), and patient selection for the most adequate treatment.

Dataset Information

Current treatments and novel therapeutic targets for castration resistant prostate cancer with bone metastasis.

Publications

Current treatments and novel therapeutic targets for castration resistant prostate cancer with bone metastasis.

Similar Datasets

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