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New and emerging therapies for bone metastases in genitourinary cancers.

ABSTRACT: Bone metastases are a common feature of advanced genitourinary malignancies and a prominent cause of morbidity and mortality.The objective of this review is to discuss the incidence, pathophysiology, and management of bone metastases in the most prevalent genitourinary malignancies.We reviewed the relevant medical literature, with a particular emphasis on prospective randomized controlled trials. Much of the relevant clinical trial data focus on prostate cancer (PCa). We provide a nonsystematic review and our perspective on the available data.Clinical manifestations can include pain, hypercalcemia, pathologic fractures, and spinal cord compression. Optimal systemic therapy for skeletal metastases often features a combination of disease-specific therapy and bone-targeted therapy. Some agents, such as the radiopharmaceutical radium-223, blur the line between those categories. Osteoclast inhibition is a validated strategy in the management of selected patients with bone metastases. Zoledronic acid, a bisphosphonate, is approved for the prevention of skeletal events caused by solid tumors metastatic to bone. Denosumab is a fully human monoclonal antibody that inactivates receptor activator of nuclear factor-?B ligand and is approved for the same indication. Beta-emitting radiopharmaceuticals can be effective for the palliation of pain caused by bone metastases, but their use is often limited by marrow suppression. The alpha-emitting radiopharmaceutical radium-223 has recently been shown to improve overall survival and prevent skeletal events in select men with castration-resistant PCa metastatic to bone. Multiple ongoing clinical trials are designed to examine the potential for therapeutic inhibition of additional targets such as Src and hepatocyte growth factor (MET).Bone metastases cause considerable morbidity and mortality among patients with genitourinary malignancies. Optimal management requires consideration of bone-targeted therapy as well as disease-specific therapy. Further research is needed to optimize the use of existing agents and to define the therapeutic potential of novel targets.

SUBMITTER: Saylor PJ

PROVIDER: S-EPMC3661203 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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New and emerging therapies for bone metastases in genitourinary cancers.

Saylor Philip J PJ Armstrong Andrew J AJ Fizazi Karim K Freedland Stephen S Saad Fred F Smith Matthew R MR Tombal Bertrand B Pienta Kenneth K

European urology 20121123 2

<h4>Context</h4>Bone metastases are a common feature of advanced genitourinary malignancies and a prominent cause of morbidity and mortality.<h4>Objective</h4>The objective of this review is to discuss the incidence, pathophysiology, and management of bone metastases in the most prevalent genitourinary malignancies.<h4>Evidence acquisition</h4>We reviewed the relevant medical literature, with a particular emphasis on prospective randomized controlled trials. Much of the relevant clinical trial d ...[more]

PMID: 23201471

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Project description:Sex-associated differences in bone metastasis formation from breast, lung, and prostate cancer exist in clinical studies, but have not been systematically reviewed. Differences in the bone marrow niche can be attributed to sexual dimorphism, to genetic variations that affect sex hormone levels, or to the direct effects of sex hormones, natural or exogenously delivered. This review describes the present understanding of sex-associated and sex hormone level differences in the marrow niche and in formation of bone metastasis during the transition of these three cancers from treatable disease to an often untreatable, lethal metastatic one. Our purpose is to provide insight into some underlying molecular mechanisms for hormonal influence in bone metastasis formation, and to the potential influence of sexual dimorphism, genetic differences affecting sex assignment, and sex hormone level differences on the bone niche and its favorability for metastasis formation. We reviewed publications in PubMed and EMBASE, including full length manuscripts, case reports, and clinical studies of relevance to our topic. We focused on bone metastasis formation in breast, lung, and prostate cancer because all three commonly present with bone metastases. Several clear observations emerged. For breast cancer bone metastasis formation, estrogen receptor (ER) signaling pathways indicate a role for ER beta (ERβ). Estrogen influences the bone microenvironment, creating and conditioning a favorable niche for colonization and breast cancer progression. For lung cancer, studies support the hypothesis that females have a more favorable bone microenvironment for metastasis formation. For prostate cancer, a decrease in the relative androgen to estrogen balance or a "feminization" of bone marrow favors bone metastasis formation, with a potentially important role for ERβ that may be similar to that in breast cancer. Long-term estrogen administration or androgen blockade in males may feminize the bone marrow niche to one more favorable for bone metastases in prostate cancer. Administration of androgens in females, especially combined with mastectomy, may reduce risk of developing bone metastatic breast cancer. We conclude that it should be considered that females, those with female-leaning genetic variations, or hormonal states that feminize the bone marrow, may offer favorable sites for bone metastases.

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New and emerging therapies for bone metastases in genitourinary cancers.

Publications

New and emerging therapies for bone metastases in genitourinary cancers.

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