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treatment sequencing bone metastasis prostate

Wei-Hua Li, Hao-Jie Wu, Yu-Xia Li, Hua-Gang Pan, Tao Meng, Xiao Wang
Osteosarcoma is the most common malignant bone tumor. In recent years, although a lot of research in the mechanism of osteosarcoma development and metastasis had been done, the molecular mechanisms are still elusive. MicroRNAs (miRs), as small noncoding RNA sequences, are dysregulated in various diseases, including cancer, negatively modulating the target genes expression by posttranscriptional repression. MicroRNA-143 (miR-143) has been reported to be reduced in cancers, including pituitary, colorectal, prostate cancer and cervical...
May 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jong Chul Park, Mario A Eisenberger
During the past several years, there has been substantial progress in the development of treatments for advanced prostate cancer with the approval of multiple new life-prolonging agents using different mechanisms of action. Such progress was attainable because of advances in our understanding of the biology behind mechanisms of androgen receptor pathway activation, complex tumor-microenvironment interaction of bone metastasis, antitumor immunology, and new oncogenic pathways. Continuous efforts are being made to develop new therapeutics with novel mechanisms of action, define the optimal sequences and/or combinations of current agents, and identify reliable surrogate end points to facilitate new drug development...
December 2015: Mayo Clinic Proceedings
Antonio Luna, Joan C Vilanova, Lidia Alcalá Mata
Bone metastases are a recognized prognostic factor in patients with prostate cancer. Currently, Tc99 bone scan is the most frequently used imaging technique for their detection, showing a high sensitivity but a limited specificity. Thus, new morphological and mainly functional imaging techniques based on PET and MRI, or hybrid techniques such as PET-CT or PET-MRI have been introduced to improve metastases detection, estimation of total tumor load and for therapeutic monitoring. In this clinical scenario, total body MRI has arisen as a very promising technique in detection and therapeutic monitoring of bone metastases of prostate cancer, because it neither uses ionizing radiation nor needs the administration of contrast media...
April 2015: Archivos Españoles de Urología
C Kontaxis, G H Bol, J J W Lagendijk, B W Raaymakers
The MRI linear accelerator (MR-linac) that is currently being installed in the University Medical Center Utrecht (Utrecht, The Netherlands), will be able to track the patient's target(s) and Organ(s) At Risk during radiation delivery. In this paper, we present a treatment planning system for intensity-modulated radiotherapy (IMRT). It is capable of Adaptive Radiotherapy and consists of a GPU Monte Carlo dose engine, an inverse dose optimization algorithm and a novel adaptive sequencing algorithm. The system is able to compensate for patient anatomy changes and enables radiation delivery immediately from the first calculated segment...
March 21, 2015: Physics in Medicine and Biology
Takashi Kobayashi, Osamu Ogawa
Following mile stone discoveries of ETS family-associated gene fusion and splicing variant of androgen receptor, next generation sequencing (NGS) has been rapidly introduced to prostate cancer research and already provided several important information on genomic alteration of the disease. Those mutational landscapes demonstrated the generally lower mutation rate through treatment-naive to lethal castration resistant stages compared to other major malignant diseases and implicated distinct pathomechanisms with regard to the presence of ETS family-associated gene fusion...
December 2014: Nihon Rinsho. Japanese Journal of Clinical Medicine
Jeremy S Frieling, David Basanta, Conor C Lynch
BACKGROUND: A paucity of therapeutic options is available to treat men with metastatic castration-resistant prostate cancer (mCRPC). However, recent developments in our understanding of the disease have resulted in several new therapies that show promise in improving overall survival rates in this patient population. METHODS: Agents approved for use in the United States and those undergoing clinical trials for the treatment of mCRPC are reviewed. Recent contributions to the understanding of prostate biology and bone metastasis are discussed as well as how the underlying mechanisms may represent opportunities for therapeutic intervention...
January 2015: Cancer Control: Journal of the Moffitt Cancer Center
Ethan Basch, D Andrew Loblaw, Thomas K Oliver, Michael Carducci, Ronald C Chen, James N Frame, Kristina Garrels, Sebastien Hotte, Michael W Kattan, Derek Raghavan, Fred Saad, Mary-Ellen Taplin, Cindy Walker-Dilks, James Williams, Eric Winquist, Charles L Bennett, Ted Wootton, R Bryan Rumble, Stacie B Dusetzina, Katherine S Virgo
PURPOSE: To provide treatment recommendations for men with metastatic castration-resistant prostate cancer (CRPC). METHODS: The American Society of Clinical Oncology and Cancer Care Ontario convened an expert panel to develop evidence-based recommendations informed by a systematic review of the literature. RESULTS: When added to androgen deprivation, therapies demonstrating improved survival, improved quality of life (QOL), and favorable benefit-harm balance include abiraterone acetate/prednisone, enzalutamide, and radium-223 ((223)Ra; for men with predominantly bone metastases)...
October 20, 2014: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Yusuf Tutar
Human genome sequencing was started to solve four letter algorithm of the genome to understand the complex nature of human metabolism. However, after completion of Human Genome Project many scientists realized that sequence information alone was not sufficient to solve the biochemical mechanism of the organism through classical approaches. Non-coding parts of the genome produce small conserved ribonucleic acids, miRNAs to control cellular and physiological processes [1, 2]. This breakthrough discovery directed researches to examine role of miRNA in cancer since miRNAs are involved in the development, cell differentiation, and regulation of cell cycle [3]...
2014: Current Pharmaceutical Biotechnology
Marie-Hélène Lafeuille, Jonathan Gravel, Amanda Grittner, Patrick Lefebvre, Lorie Ellis, R Scott McKenzie
BACKGROUND: Prostate cancer is the most common noncutaneous malignancy in men in the United States. Patients with metastatic castration-resistant prostate cancer (mCRPC) may be treated with secondary hormonal therapy or with chemotherapy, and potentially with concomitant corticosteroids. Corticosteroids can help manage the side effects of chemotherapy and secondary hormonal therapy and ameliorate prostate cancer-related symptoms, although corticosteroids are also associated with adverse effects...
July 2013: American Health & Drug Benefits
Miaojun Zhu, Qin Chen, Xin Liu, Qian Sun, Xian Zhao, Rong Deng, Yanli Wang, Jian Huang, Ming Xu, Jianshe Yan, Jianxiu Yu
Prostate cancer is a leading cause of cancer-related mortality in men worldwide and there is a lack of effective treatment options for advanced (metastatic) prostate cancer. Currently, limited knowledge is available concerning the role of long non-coding RNAs in prostate cancer metastasis. In this study, we found that long non-coding RNA H19 (H19) and H19-derived microRNA-675 (miR-675) were significantly downregulated in the metastatic prostate cancer cell line M12 compared with the non-metastatic prostate epithelial cell line P69...
August 2014: FEBS Journal
Curtis R Warren, Brian J Grindel, Lewis Francis, Daniel D Carson, Mary C Farach-Carson
Perlecan/HSPG2, a heparan sulfate proteoglycan typically found at tissue borders including those separating epithelia and connective tissue, increases near sites of invasion of primary prostatic tumors as previously shown for other proteins involved in desmoplastic tissue reaction. Studies of prostate cancer cells and stromal cells from both prostate and bone, the major site for prostate cancer metastasis, showed that cancer cells and a subset of stromal cells increased production of perlecan in response to cytokines present in the tumor microenvironment...
July 2014: Journal of Cellular Biochemistry
Sebastian Christoph Schmid, Alexander Geith, Alena Böker, Robert Tauber, Anna Katharina Seitz, Markus Kuczyk, Christoph von Klot, Jürgen Erich Gschwend, Axel Stuart Merseburger, Margitta Retz
INTRODUCTION: Enzalutamide is a novel antiandrogen which is approved for the treatment of metastatic, castration-resistant prostate cancer (mCRPC) after taxane-based chemotherapy. The efficacy of enzalutamide after the sequence docetaxel and abiraterone is not proven. METHODS: Thirty-five mCRPC patients in the German compassionate use program, who received enzalutamide after progression with taxane-based chemotherapy and abiraterone were prospectively evaluated...
February 2014: Advances in Therapy
Rahul Aggarwal, Susan Halabi, William Kevin Kelly, Daniel George, John F Mahoney, Frederick Millard, Walter M Stadler, Michael J Morris, Philip Kantoff, J Paul Monk, Michael Carducci, Eric J Small
BACKGROUND: Preliminary data suggest a potential decreased benefit of docetaxel in patients with metastatic, castration-resistant prostate cancer (mCRPC) who previously received abiraterone acetate, a novel androgen synthesis inhibitor (ASI). Cancer and Leukemia Group B (CALGB) trial 90401 (Alliance), a phase 3 trial in patients with mCRPC who received docetaxel-based chemotherapy, offered the opportunity to evaluate effect of prior ketoconazole, an earlier generation ASI, on clinical outcomes after docetaxel...
October 15, 2013: Cancer
Lina Yin, Qingzhong Hu, Rolf W Hartmann
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...
2013: International Journal of Molecular Sciences
D A Loblaw, C Walker-Dilks, E Winquist, S J Hotte
AIMS: Since 2004, docetaxel-based chemotherapy has been the standard of care for men with metastatic castration-resistant prostate cancer (mCRPC), but recently randomised controlled trials (RCTs) of novel agents have shown promise in extending overall survival. These trials have evaluated agents delivered before chemotherapy, to replace or supplement docetaxel, or addressed treatment options for men who have progressed on docetaxel therapy. This review was undertaken to determine which systemic therapies improve cancer- or patient-related outcomes in men with mCRPC...
July 2013: Clinical Oncology: a Journal of the Royal College of Radiologists
Michael R Harrison, Terence Z Wong, Andrew J Armstrong, Daniel J George
BACKGROUND: Radium-223 chloride ((223)Ra; Alpharadin) is an alpha-emitting radioisotope that targets areas of osteoblastic metastasis and is excreted by the small intestine. When compared with beta-emitters (eg, strontium-89, samarium-153), (223)Ra delivers a high quantity of energy per track length with short tissue penetration. OBJECTIVE: This review describes the mechanism, radiobiology, and preclinical development of (223)Ra and discusses the clinical data currently available regarding its safety and efficacy profile...
2013: Cancer Management and Research
Dow-Mu Koh, Aslam Sohaib
Diffusion-weighted magnetic resonance (MR) imaging (DWI) is now widely incorporated as a standard MR imaging sequence for the assessment of the male pelvis. DWI can improve the detection, characterization, and staging of pelvic malignancies, such as prostate, bladder, and rectal cancers. There is growing interest in applying quantitative DWI for the assessment of tumor treatment response. In addition, the technique seems promising for the evaluation of metastatic nodal and bone disease in the pelvis.
November 2012: Radiologic Clinics of North America
Yuhsaku Kanoh, Hideki Ohtani, Shin Egawa, Shiro Baba, Tohru Akahoshi
α2-Macroglobulin (α2M) is thought to be involved in cancer metastasis and inflammatory reaction through its functions as a proteinase inhibitor and carrier protein for interleukin-6 (IL-6). We previously reported that advanced prostate cancer (PCa) patients with multiple distant bone metastases had markedly decreased serum α2M levels (<20 mg/dl) and no detection of α2M by immunoelectrophoresis (defined as α2M deficiency). We also showed a relationship between serum α2M levels and acute inflammatory biomarkers in PCa patients with or without α2M deficiency...
July 2012: International Journal of Oncology
Howard I Scher, Michael J Morris, Ethan Basch, Glenn Heller
New therapeutic approaches for castration-resistant prostate cancer (CRPC) introduce new treatment dilemmas: how best to sequence these options to maximally benefit patients, what tests to perform before and after treatment to assess disease status, and how to interpret the test results and use them to guide treatment. New and specific end points for different classes of drugs are needed to provide the information to guide these treatment decisions. In 2008, the Prostate Cancer Working Group 2 consensus criteria for early-phase clinical trials redefined clinical trial end points as first, to control, relieve, or eliminate disease manifestations present when treatment is started and second, to prevent or delay future disease manifestations...
September 20, 2011: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Mehran Salehpour, Karl Håkansson, Urban Höglund, Annika Grahn-Westin, Sten Nilsson, Marcela Márquez, Göran Possnert, Anders R Holmberg
Data on the use of accelerator mass spectrometry (AMS) in conjunction with in vivo studies of macromolecular drugs are scarce. The present study shows the versatility of this technique when investigating the pharmacokinetics (PK) of a macromolecular drug candidate, a polybisphosphonate conjugate (ODX). The aforementioned is a polymer (molecular weight ~30 kDa) constituting a carbohydrate backbone with covalently linked ligands (aldendronate and aminoguanidine) and is intended for treatment of osteoporosis and the therapy of bone metastasis from prostate cancer...
September 15, 2011: Rapid Communications in Mass Spectrometry: RCM
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