Abstract 46: A new class of precision therapeutics that inhibit prostate cancer mediated bone destruction

Prostate cancer (PC) is one of the most common cancers arising in men and has a high propensity for bone metastasis, particularly to the spine. At this stage, it often causes severe morbidity due to pathological fracture and/or metastatic epidural spinal cord compression which, if untreated, inevitably leads to intractable pain, neurological deficit, and paralysis. Unfortunately, the underlying molecular mechanisms driving growth of secondary PC in the bony vertebral column remain largely unknown. Further investigation is warranted in order to identify therapeutic targets in the future. This review summarizes the current understanding of PC bone metastasis in the spine, highlighting interactions between key tumor and bone-derived factors which influence tumor progression, especially the functional roles of osteoblasts and osteoclasts in the bone microenvironment through their interactions with metastatic PC cells and the critical pathway RANK/RANKL/OPG in bone destruction.

Download Full-text

A new class of inhibitors of 2-arachidonoylglycerol hydrolysis and invasion of prostate cancer cells

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2005.05.049 ◽

2005 ◽

Vol 332 (4) ◽

pp. 1028-1033 ◽

Cited By ~ 34

Author(s):

Kasem Nithipatikom ◽

Michael P. Endsley ◽

Marilyn A. Isbell ◽

Craig E. Wheelock ◽

Bruce D. Hammock ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Prostate Cancer Cells ◽

New Class

Download Full-text

Biomarker Potential of Plasma MicroRNA-150-5p in Prostate Cancer

Medicina ◽

10.3390/medicina55090564 ◽

2019 ◽

Vol 55 (9) ◽

pp. 564 ◽

Cited By ~ 2

Author(s):

Ionut Andrei Paunescu ◽

Razvan Bardan ◽

Anca Marcu ◽

Diana Nitusca ◽

Alis Dema ◽

...

Keyword(s):

Prostate Cancer ◽

Area Under The Curve ◽

Plasma Samples ◽

Tissue Samples ◽

New Class ◽

Non Invasive ◽

Plasma Microrna ◽

Cancer Tissues ◽

Tissue Cancer

Background and Objectives: Over decades, prostate cancer (PCa) has become one of the leading causes of cancer mortality in men. Extensive evidence exists that microRNAs (miRNAs or miRs) are key players in PCa and a new class of non-invasive cancer biomarkers. Materials and Methods: We performed miRNA profiling in plasma and tissues of PCa patients and attempted the validation of candidate individual miRs as biomarkers. Results: The comparison of tissue and plasma profiling results revealed five commonly dysregulated miRs, namely, miR-130a-3p, miR-145-5p, miR-148a-3p, miR-150-5p, and miR-365a-3p, of which only three show concordant changes—miR-130a-3p and miR-150-5p were downregulated and miR-148a-3p was upregulated in both tissue and plasma samples, respectively. MiR-150-5p was validated as significantly downregulated in both plasma and tissue cancer samples, with a fold change of −2.697 (p < 0.001), and −1.693 (p = 0.035), respectively. ROC analysis showed an area under the curve (AUC) of 0.817 (95% CI: 0.680–0.995) for plasma samples and 0.809 (95% CI: 0.616–1.001) for tissue samples. Conclusions: We provide data indicating that miR-150-5p plasma variations in PCa patients are associated with concordant changes in prostate cancer tissues; however, given the heterogeneous nature of previous findings of miR-150-5p expression in PCa cells, additional future studies of a larger sample size are warranted in order to confirm the biomarker potential and role of miRNA-150-5p in PCa biology.

Download Full-text

Effects of Denosumab versus Zoledronic Acid in Patients with Castration-Resistant Prostate Cancer and Bone Metastases

Oncology & Hematology Review (US) ◽

10.17925/ohr.2012.08.2.94 ◽

2012 ◽

Vol 08 (02) ◽

pp. 94 ◽

Cited By ~ 1

Author(s):

Neal Shore ◽

Carsten Goessl ◽

◽

Keyword(s):

Prostate Cancer ◽

Zoledronic Acid ◽

Bone Metastases ◽

Human Monoclonal Antibody ◽

Bone Destruction ◽

Comprehensive Treatment ◽

Castration Resistant Prostate Cancer ◽

Efficacy Analysis ◽

Castration Resistant ◽

Skeletal Complications

Progression of castration-resistant prostate cancer often leads to bone metastases, increasing the risk of skeletal-related events (SREs). The use of antiresorptive therapies such as denosumab, a human monoclonal antibody and zoledronic acid (ZA), a bisphosphonate, reduces bone destruction by inhibiting osteoclast function and survival. In 2002, ZA was approved for the prevention of skeletal complications in patients with bone disease from myeloma or bone metastases from solid tumors including prostate cancer. Recently, efficacy analysis demonstrated superiority of denosumab to ZA for the prevention or delay of SREs in 1,901 patients with prostate cancer and bone metastases, significantly delaying the time to first SRE and time to first and subsequent SRE compared to ZA. Decreases in bone turnover markers were greater with denosumab, mirroring the reduction in SREs. The reported incidence of adverse events were similar between denosumab and ZA. Advanced prostate cancer patients require long-term disease management where maintenance of overall bone health is an essential component of a comprehensive treatment program.

Download Full-text

Diacylglycerol (DAG)-lactones, a New Class of Protein Kinase C (PKC) Agonists, Induce Apoptosis in LNCaP Prostate Cancer Cells by Selective Activation of PKCα

Journal of Biological Chemistry ◽

10.1074/jbc.m107639200 ◽

2001 ◽

Vol 277 (1) ◽

pp. 645-655 ◽

Cited By ~ 68

Author(s):

Maria Laura Garcia-Bermejo ◽

Federico Coluccio Leskow ◽

Teruhiko Fujii ◽

Qiming Wang ◽

Peter M. Blumberg ◽

...

Keyword(s):

Prostate Cancer ◽

Protein Kinase C ◽

Protein Kinase ◽

Cancer Cells ◽

Prostate Cancer Cells ◽

Selective Activation ◽

New Class ◽

Kinase C

Download Full-text

Abrogation of prostaglandin E-EP4 signaling in osteoblasts prevents the bone destruction induced by human prostate cancer metastases

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2016.07.075 ◽

2016 ◽

Vol 478 (1) ◽

pp. 154-161

Author(s):

Kenta Watanabe ◽

Tsukasa Tominari ◽

Michiko Hirata ◽

Chiho Matsumoto ◽

Takayuki Maruyama ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Destruction ◽

Human Prostate ◽

Prostaglandin E ◽

Human Prostate Cancer ◽

Cancer Metastases

Download Full-text

Imidazole substituted biphenyls: A new class of highly potent and in vivo active inhibitors of P450 17 as potential therapeutics for treatment of prostate cancer

Bioorganic & Medicinal Chemistry ◽

10.1016/s0968-0896(99)00160-1 ◽

1999 ◽

Vol 7 (9) ◽

pp. 1913-1924 ◽

Cited By ~ 36

Author(s):

Bertil G. Wachall ◽

Markus Hector ◽

Yan Zhuang ◽

Rolf W. Hartmann

Keyword(s):

Prostate Cancer ◽

New Class ◽

Potential Therapeutics

Download Full-text

Topical Treatment with Xiaozheng Zhitong Paste (XZP) Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/215892 ◽

2015 ◽

Vol 2015 ◽

pp. 1-14 ◽

Cited By ~ 2

Author(s):

Yanju Bao ◽

Yebo Gao ◽

Maobo Du ◽

Wei Hou ◽

Liping Yang ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Pain ◽

Structural Damage ◽

Bone Pain ◽

Bone Destruction ◽

Bone Cancer ◽

Bone Cancer Pain ◽

Osteoblast Activity ◽

Mechanical Threshold ◽

Bone Damage

To explore the effects and mechanisms of Xiaozheng Zhitong Paste (XZP) on bone cancer pain, Wistar rats were inoculated with vehicle or prostate cancer PC-3 into the tibia bone and treated topically with inert paste, XZP at 15.75, 31.5, or 63 g/kg twice per day for 21 days. Their bone structural damage, nociceptive behaviors, bone osteoclast and osteoblast activity, and the levels of OPG, RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-αwere examined. In comparison with that in the placebo group, significantly reduced numbers of invaded cancer cells, decreased levels of bone damage and mechanical threshold and paw withdrawal latency, lower levels of serum TRACP5b, ICTP, PINP, and BAP, and less levels of bone osteoblast and osteoclast activity were detected in the XZP-treated rats (P<0.05). Moreover, significantly increased levels of bone OPG but significantly decreased levels of RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-αwere detected in the XZP-treated rats (P<0.05for all). Together, XZP treatment significantly mitigated the cancer-induced bone damage and bone osteoclast and osteoblast activity and alleviated prostate cancer-induced bone pain by modulating the RANKL/RANK/OPG pathway and bone cancer-related inflammation in rats.

Download Full-text