Molecular genetics of prostate cancer: new prospects for old challenges
Michael M. Shen,Cory Abate-Shen +1 more
TLDR
An overview of major themes in prostate cancer research is presented, focusing on current knowledge of principal events in cancer initiation and progression, including new insights into the mechanisms of castration resistance, identification of stem cells and tumor-initiating cells, and development of mouse models for preclinical evaluation of novel therapuetics.Abstract:
Despite much recent progress, prostate cancer continues to represent a major cause of cancer-related mortality and morbidity in men. Since early studies on the role of the androgen receptor that led to the advent of androgen deprivation therapy in the 1940s, there has long been intensive interest in the basic mechanisms underlying prostate cancer initiation and progression, as well as the potential to target these processes for therapeutic intervention. Here, we present an overview of major themes in prostate cancer research, focusing on current knowledge of principal events in cancer initiation and progression. We discuss recent advances, including new insights into the mechanisms of castration resistance, identification of stem cells and tumor-initiating cells, and development of mouse models for preclinical evaluation of novel therapuetics. Overall, we highlight the tremendous research progress made in recent years, and underscore the challenges that lie ahead.read more
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Journal ArticleDOI
The mutational landscape of lethal castration-resistant prostate cancer
Catherine S. Grasso,Yi-Mi Wu,Dan R. Robinson,Xuhong Cao,Saravana M. Dhanasekaran,Amjad Khan,Michael J. Quist,Xiaojun Jing,Robert J. Lonigro,J. Chad Brenner,Irfan A. Asangani,Bushra Ateeq,Sang Y. Chun,Javed Siddiqui,Lee Sam,Matt Anstett,Rohit Mehra,John R. Prensner,Nallasivam Palanisamy,Gregory A. Ryslik,Fabio Vandin,Benjamin J. Raphael,Lakshmi P. Kunju,Daniel R. Rhodes,Kenneth J. Pienta,Arul M. Chinnaiyan,Scott A. Tomlins +26 more
TL;DR: The mutational landscape of a heavily treated metastatic cancer is described, novel mechanisms of AR signalling deregulated in prostate cancer are identified, and candidates for future study are prioritize.
Journal ArticleDOI
Punctuated Evolution of Prostate Cancer Genomes
Sylvan C. Baca,Davide Prandi,Michael S. Lawrence,Juan Miguel Mosquera,Alessandro Romanel,Yotam Drier,Yotam Drier,Kyung Park,Naoki Kitabayashi,Theresa Y. MacDonald,Mahmoud Ghandi,Eliezer M. Van Allen,Eliezer M. Van Allen,Gregory V. Kryukov,Gregory V. Kryukov,Gregory V. Kryukov,Andrea Sboner,Jean-Philippe Theurillat,David Soong,Elizabeth Nickerson,Daniel Auclair,Ashutosh K. Tewari,Himisha Beltran,Robert C. Onofrio,Gunther Boysen,Candace Guiducci,Christopher E. Barbieri,Kristian Cibulskis,Andrey Sivachenko,Scott L. Carter,Gordon Saksena,Douglas Voet,Alex H. Ramos,Alex H. Ramos,Wendy Winckler,Michelle Cipicchio,Kristin G. Ardlie,Philip W. Kantoff,Michael F. Berger,Stacey Gabriel,Todd R. Golub,Matthew Meyerson,Eric S. Lander,Olivier Elemento,Gad Getz,Francesca Demichelis,Francesca Demichelis,Mark A. Rubin,Levi A. Garraway +48 more
TL;DR: In this paper, the genesis of genomic rearrangements, including abundant DNA translocations and deletions that arise in a highly interdependent manner, was modeled and shown to induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution.
Journal ArticleDOI
Identification of Multipotent Luminal Progenitor Cells in Human Prostate Organoid Cultures
Wouter R. Karthaus,Phillip J. Iaquinta,Jarno Drost,Ana Gracanin,Ruben van Boxtel,John Wongvipat,Catherine Dowling,Dong Gao,Harry Begthel,Norman Sachs,Robert G.J. Vries,Edwin Cuppen,Yu Chen,Charles L. Sawyers,Charles L. Sawyers,Hans Clevers +15 more
TL;DR: A 3D culture system that supports long-term expansion of primary mouse and human prostate organoids, composed of fully differentiated CK5+ basal and CK8+ luminal cells is described, which supports a luminal multilineage progenitor cell model for prostate tissue and establishes a robust, scalable system for mechanistic studies.
Journal ArticleDOI
Effective combinatorial immunotherapy for castration-resistant prostate cancer.
Xin Lu,James W. Horner,Erin Paul,Xiaoying Shang,Patricia Troncoso,Pingna Deng,Shan Jiang,Qing Chang,Denise J. Spring,Padmanee Sharma,John A. Zebala,Dean Y. Maeda,Y. Alan Wang,Ronald A. DePinho +13 more
TL;DR: A novel chimaeric mouse model of mCRPC is developed to efficiently test combination therapies in an autochthonous setting and illuminate a clinical path hypothesis for combining immune checkpoint blockade with MDSC-targeted therapies in the treatment of m CRPC.
Journal ArticleDOI
Genetics and biology of prostate cancer.
TL;DR: Improved disease management will also benefit from artificial intelligence-based expert decision support systems for proper standard of care, prognostic determinant biomarkers to minimize overtreatment of localized disease, and new standards of care accelerated by next-generation adaptive clinical trials.
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TL;DR: When given with prednisone, treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain, serum PSA level, and quality of life, as compared with mitoxantrone plusprednisone.
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