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Overcoming Drug Resistance and Treating Advanced Prostate Cancer

Most of the prostate cancers (PCa) in advanced stage will progress to castration-resistant prostate cancer (CRPC). Within CRPC group, 50-70% of the patients will develop bone metastasis in axial and other regions of the skeleton. Once PCa cells spread to the bone, currently, no treatment regimens ar...

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Autores principales: Semenas, Julius, Allegrucci, Cinzia, Boorjian, Stephen A, Mongan, Nigel P, Persson, Jenny Liao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bentham Science Publishers 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474961/
https://www.ncbi.nlm.nih.gov/pubmed/22746994
http://dx.doi.org/10.2174/138945012802429615
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author Semenas, Julius
Allegrucci, Cinzia
Boorjian, Stephen A
Mongan, Nigel P
Persson, Jenny Liao
author_facet Semenas, Julius
Allegrucci, Cinzia
Boorjian, Stephen A
Mongan, Nigel P
Persson, Jenny Liao
author_sort Semenas, Julius
collection PubMed
description Most of the prostate cancers (PCa) in advanced stage will progress to castration-resistant prostate cancer (CRPC). Within CRPC group, 50-70% of the patients will develop bone metastasis in axial and other regions of the skeleton. Once PCa cells spread to the bone, currently, no treatment regimens are available to eradicate the metastasis, and cancer-related death becomes inevitable. In 2012, it is estimated that there will be 28,170 PCa deaths in the United States. Thus, PCa bone metastasis-associated clinical complications and treatment resistance pose major clinical challenges. In this review, we will present recent findings on the molecular and cellular pathways that are responsible for bone metastasis of PCa. We will address several novel mechanisms with a focus on the role of bone and bone marrow microenvironment in promoting PCa metastasis, and will further discuss why prostate cancer cells preferentially metastasize to the bone. Additionally, we will discuss novel roles of several key pathways, including angiogenesis and extracellular matrix remodeling in bone marrow and stem cell niches with their relationship to PCa bone metastasis and poor treatment response. We will evaluate how various chemotherapeutic drugs and radiation therapies may allow aggressive PCa cells to gain advantageous mutations leading to increased survival and rendering the cancer cells to become resistant to treatment. The novel concept relating several key survival and invasion signaling pathways to stem cell niches and treatment resistance will be reviewed. Lastly, we will provide an update of several recently developed novel drug candidates that target metastatic cancer microenvironments or niches, and discuss the advantages and significance provided by such therapeutic approaches in pursuit of overcoming drug resistance and treating advanced PCa.
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spelling pubmed-34749612012-10-22 Overcoming Drug Resistance and Treating Advanced Prostate Cancer Semenas, Julius Allegrucci, Cinzia Boorjian, Stephen A Mongan, Nigel P Persson, Jenny Liao Curr Drug Targets Article Most of the prostate cancers (PCa) in advanced stage will progress to castration-resistant prostate cancer (CRPC). Within CRPC group, 50-70% of the patients will develop bone metastasis in axial and other regions of the skeleton. Once PCa cells spread to the bone, currently, no treatment regimens are available to eradicate the metastasis, and cancer-related death becomes inevitable. In 2012, it is estimated that there will be 28,170 PCa deaths in the United States. Thus, PCa bone metastasis-associated clinical complications and treatment resistance pose major clinical challenges. In this review, we will present recent findings on the molecular and cellular pathways that are responsible for bone metastasis of PCa. We will address several novel mechanisms with a focus on the role of bone and bone marrow microenvironment in promoting PCa metastasis, and will further discuss why prostate cancer cells preferentially metastasize to the bone. Additionally, we will discuss novel roles of several key pathways, including angiogenesis and extracellular matrix remodeling in bone marrow and stem cell niches with their relationship to PCa bone metastasis and poor treatment response. We will evaluate how various chemotherapeutic drugs and radiation therapies may allow aggressive PCa cells to gain advantageous mutations leading to increased survival and rendering the cancer cells to become resistant to treatment. The novel concept relating several key survival and invasion signaling pathways to stem cell niches and treatment resistance will be reviewed. Lastly, we will provide an update of several recently developed novel drug candidates that target metastatic cancer microenvironments or niches, and discuss the advantages and significance provided by such therapeutic approaches in pursuit of overcoming drug resistance and treating advanced PCa. Bentham Science Publishers 2012-09 2012-09 /pmc/articles/PMC3474961/ /pubmed/22746994 http://dx.doi.org/10.2174/138945012802429615 Text en © 2012 Bentham Science Publishers http://creativecommons.org/licenses/by/2.5/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Semenas, Julius
Allegrucci, Cinzia
Boorjian, Stephen A
Mongan, Nigel P
Persson, Jenny Liao
Overcoming Drug Resistance and Treating Advanced Prostate Cancer
title Overcoming Drug Resistance and Treating Advanced Prostate Cancer
title_full Overcoming Drug Resistance and Treating Advanced Prostate Cancer
title_fullStr Overcoming Drug Resistance and Treating Advanced Prostate Cancer
title_full_unstemmed Overcoming Drug Resistance and Treating Advanced Prostate Cancer
title_short Overcoming Drug Resistance and Treating Advanced Prostate Cancer
title_sort overcoming drug resistance and treating advanced prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474961/
https://www.ncbi.nlm.nih.gov/pubmed/22746994
http://dx.doi.org/10.2174/138945012802429615
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