Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone metastases and their associated morbidities are common in patients with advanced prostate cancer and other genitourinary (GU) malignancies. Zoledronic acid> (a bisphosphonate) has long been the mainstay of treatment for reducing the risk of skeletal-related events in patients with bone metastases from GU cancers, and denosumab (a monoclonal antibody directed against the receptor activator of nuclear factor kappa B ligand [RANKL]) has recently received approval for this indication in the United States. Preclinical data indicate that modifying the bone microenvironment may render it less conducive to metastasis, and emerging clinical findings suggest that the potential benefits from bone-directed therapies are not limited to reducing skeletal morbidity-these agents might help to improve survival and delay bone disease progression or even development of bone metastases (if used earlier in the disease course). This chapter reviews the rationale and recent clinical data supporting an antimetastatic role for bone-directed therapies in patients with GU malignancies.
 ...
PMID:Bisphosphonates: prevention of bone metastases in prostate cancer. 2230 72

Bone metastasis is a debilitating side effect of advanced prostatic carcinoma impacting nearly all of the men developing this disease. Even though a majority of these lesions are considered osteoblastic, it is believed that there is an underlying osteolytic component. Lytic processes are governed primarily by osteoclasts, the primary bone resorptive cell. Osteolysis has been implicated in tumor cell seeding and nourishment of tumor growth via development of pro-tumorigenic changes in the microenvironment. Herein, we provide a current view of the processes involved in regulating osteolysis in the presence of prostate cancer bone metastases. Several factors have been implicated in the division, differentiation, and activation of osteoclasts, including, but not limited to, interleukin-6, receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), and parathyroid hormone-related protein (PTHrP). Effector molecules in bone resorption play a significant role, such as matrix metalloproteinases (MMPs), cathepsins, and acid secretion. The primary method for treating skeletal events associated with prostate cancer bone metastases has been bisphosphonates. However, a new therapeutic, denosumab, a monoclonal antibody that inhibits RANKL in a mechanism similar to that attributed to the endogenous mediator OPG, has received approval for treatment of skeletally associated metastases. Additional novel targets are continuously being developed for bone metastases. In this review, we describe the processes involved in osteolysis of the prostate cancer bone microenvironment, and introduce therapeutics that may play a role in inhibiting tumor growth leading to increased survival and quality of life.
 ...
PMID:Understanding and targeting osteoclastic activity in prostate cancer bone metastases. 2306 77

Since 2010, six drugs have been approved for the treatment of castration-resistant prostate cancer, i.e., CYP17 inhibitor Abiraterone, androgen receptor antagonist Enzalutamide, cytotoxic agent Cabazitaxel, vaccine Sipuleucel-T, antibody Denosumab against receptor activator of nuclear factor kappa B ligand and radiopharmaceutical Alpharadin. All these drugs demonstrate improvement on overall survival, expect for Denosumab, which increases the bone mineral density of patients under androgen deprivation therapy and prolongs bone-metastasis-free survival. Besides further CYP17 inhibitors (Orteronel, Galeterone, VT-464 and CFG920), androgen receptor antagonists (ARN-509, ODM-201, AZD-3514 and EZN-4176) and vaccine Prostvac, more drug candidates with various mechanisms or new indications of launched drugs are currently under evaluation in different stages of clinical trials, including various kinase inhibitors and platinum complexes. Some novel strategies have also been proposed aimed at further potentiation of antitumor effects or reduction of side effects and complications related to treatments. Under these flourishing circumstances, more investigations should be performed on the optimal combination or the sequence of treatments needed to delay or reverse possible resistance and thus maximize the clinical benefits for the patients.
 ...
PMID:Recent progress in pharmaceutical therapies for castration-resistant prostate cancer. 2388 Aug 51

To develop new and effective chemopreventive agents against bone metastasis, we assessed the effects of muscadine grape skin extract (MSKE), whose main bioactive component is anthocyanin, on bone turnover, using prostate and breast cancer cell models overexpressing Snail transcription factor. MSKE has been shown previously to promote apoptosis in prostate cancer cells without affecting normal prostate epithelial cells. Snail is overexpressed in prostate and breast cancer, and is associated with increased invasion, migration and bone turnover/osteoclastogenesis. Cathepsin L (CatL) is a cysteine cathepsin protease that is overexpressed in cancer and involved in bone turnover. Snail overexpression in prostate (LNCaP, ARCaP-E) and breast (MCF-7) cancer cells led to increased CatL expression/activity and phosphorylated STAT-3 (pSTAT-3), compared to Neo vector controls, while the reverse was observed in C4-2 (the aggressive subline of LNCaP) cells with Snail knockdown. Moreover, CatL expression was higher in prostate and breast tumor tissue compared to normal tissue. MSKE decreased Snail and pSTAT3 expression, and abrogated Snail-mediated CatL activity, migration and invasion. Additionally, Snail overexpression promoted osteoclastogenesis, which was significantly inhibited by the MSKE as effectively as Z-FY-CHO, a CatL-specific inhibitor, or osteoprotegerin, a receptor activator of nuclear factor kappa B ligand (RANKL) antagonist. Overall, these novel findings suggest that Snail regulation of CatL may occur via STAT-3 signaling and can be antagonized by MSKE, leading to decreased cell invasion, migration and bone turnover. Therefore, inhibition using a natural product such as MSKE could potentially be a promising bioactive compound for bone metastatic cancer.
...
PMID:Muscadine grape skin extract can antagonize Snail-cathepsin L-mediated invasion, migration and osteoclastogenesis in prostate and breast cancer cells. 2606 56

Bone metastases are common in patients with advanced solid tumors, and many individuals experience debilitating skeletal-related events (SREs; e.g. pathologic fracture, hypercalcemia, radiotherapy or surgery to bone, and spinal cord compression). These events substantially affect disease outcomes, including survival and quality of life, and healthcare systems. Plain radiography is the most widely used imaging modality for the detection of bone metastases; skeletal scintigraphy, computed tomography, positron emission tomography and magnetic resonance imaging offer greater sensitivity but their use in routine practice is restricted by high costs and limited availability. Biomarkers of bone turnover may also have a role in the early detection of bone metastases and can provide valuable prognostic information on disease progression. SREs can be delayed or prevented using agents such as the receptor activator of nuclear factor kappa B ligand (RANKL) inhibitor, denosumab, and bisphosphonates. Painful bone metastases can be treated with radiofrequency ablation, radiotherapy, or radionuclides such as radium-223 dichloride, which has been shown to delay the onset of SREs in men with castration-resistant prostate cancer. Close monitoring of bone health in patients with advanced cancer may lead to early identification of individuals with bone metastases who could benefit from early intervention to prevent SREs. This review examines current guideline recommendations for assessing and monitoring bone health in patients with advanced cancer, use of biomarkers and treatment of patients with bone metastases. The emerging evidence for the potential survival benefit conferred by early intervention with denosumab and bisphosphonates is also discussed, together with best practice recommendations.
 ...
PMID:Early identification and intervention matters: A comprehensive review of current evidence and recommendations for the monitoring of bone health in patients with cancer. 2910 Jan 67


<< Previous 1 2