Journal ArticleDOI
Translational models of prostate cancer bone metastasis
Richard B Berish,Aymon Naushad Ali,Patrick G. Telmer,John A. Ronald,Hon S. Leong,Hon S. Leong +5 more
TLDR
The development of currently used models of prostate cancer bone metastasis are outlined and mechanistic and therapeutic advances made made using these models are discussed and future directions to improve the applicability of these models to the metastatic cascade and human disease are suggested.Abstract:
Metastatic disease is the principal cause of prostate-cancer-related mortality. Our ability to accurately recapitulate the spread of prostate cancer to bone - the most common site of metastasis - is critical to the development of novel metastasis-directed therapies. Several translational models of prostate cancer bone metastasis have been developed, including animal models, cell line injection models, 3D in vitro models, bone implant models, and patient-derived xenograft models. The use of these models has led to numerous advances in elucidating the molecular mechanisms of metastasis and innovations in targeted therapy. Despite this progress, current models are limited by a failure to holistically reproduce each individual element of the metastatic cascade in prostate cancer bone metastasis. In addition, factors such as accurate recapitulation of immunobiological events and improvements in tumour heterogeneity require further consideration. Knowledge gained from historical and currently used models will improve the development of next-generation models. An introspective appraisal of current preclinical models demonstrating bone metastases is warranted to narrow research focus, improve future translational modelling, and expedite the delivery of urgently needed metastasis-directed treatments.read more
Citations
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Journal ArticleDOI
Differences in Tumor Microenvironment Dictate T Helper Lineage Polarization and Response to Immune Checkpoint Therapy
Shiping Jiao,Sumit K. Subudhi,Ana Aparicio,Zhongqi Ge,Baoxiang Guan,Yuji Miura,Padmanee Sharma +6 more
TL;DR: Immune checkpoint therapy shows encouraging results in a subset of patients with metastatic castration-resistant prostate cancer (mCRPC) but still elicits a sub-optimal response among those with bone metastases, and blocking TGF-β along with ICT increases Th1 subsets and promotes clonal expansion of CD8 T cells and subsequent regression of bone CRPC and improves survival.
Journal ArticleDOI
Establishment and Characterization of Seven Dunning Rat Prostatic Cancer Cell Lines and Their Use in Developing Methods for Predicting Metastatic Abilities of Prostatic Cancers
John T. Isaacs,John T. Isaacs,William B. Isaacs,William B. Isaacs,Wouter F. J. Feitz,Wouter F. J. Feitz,Jack Scheres,Jack Scheres +7 more
TL;DR: The combination of the in vitro cell lines and their parental in vivo tumor subline will be a valuable tool for developing methods for predicting metastatic ability of prostate cancers, but no single parameter yet measured is entirely successful in making this important distinction.
Proceedings ArticleDOI
Abstract 1028: Patient-derived xenografts undergo mouse-specific tumor evolution
Uri Ben-David,Gavin Ha,Yuen-Yi Tseng,Noah F. Greenwald,Coyin Oh,Juliann Shih,James M. McFarland,Bang Wong,Jesse S. Boehm,Rameen Beroukhim,Todd R. Golub +10 more
TL;DR: Ben-David et al. as discussed by the authors monitored the dynamics of copy number alterations (CNAs) in 1,110 PDX samples across 24 cancer types, and observed rapid accumulation of CNAs during PDX passaging, often due to selection of pre-existing minor clones.
Journal ArticleDOI
Cytokines and Chemokines as Mediators of Prostate Cancer Metastasis
TL;DR: This review presents an overview of the main cytokines/chemokines, including IL-6, CXCL12, TGFβ, C XCL8, VEGF, RANKL, CCL2, Cx3CL1, IL-1,IL-7,CXCL1 and CXLI, that exert modulatory roles in prostate cancer metastasis and provides extensive description of their aberrant expression patterns in both advanced disease states and metastatic sites.
Journal ArticleDOI
Radium-223 mechanism of action: implications for use in treatment combinations
Michael J. Morris,Eva Corey,Theresa A. Guise,James L. Gulley,William Kevin Kelly,David I. Quinn,Arne Scholz,George Sgouros +7 more
TL;DR: The mechanisms through which 223Ra exerts its biological effects in metastatic castration-resistant prostate cancer are summarized, potential 223Ra combination therapies are discussed and future perspectives for targeted alpha-particle therapy are provided.
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