Journal ArticleDOI
Resistance to second-generation androgen receptor antagonists in prostate cancer.
TLDR
The use of second-generation androgen receptor antagonists (SG-ARAs) has greatly impacted the treatment of metastatic prostate cancer, providing tolerable and efficacious alternatives to chemotherapy as mentioned in this paper.Abstract:
The introduction of second-generation androgen receptor antagonists (SG-ARAs) has greatly impacted the treatment of metastatic prostate cancer, providing tolerable and efficacious alternatives to chemotherapy. SG-ARAs provide similar therapeutic benefit to abiraterone, a potent CYP17 inhibitor, and do not require the co-administration of prednisone. Despite considerable improvements in clinical outcomes in the settings of both castration sensitivity and castration resistance, the durability of clinical response to the SG-ARAs enzalutamide, apalutamide and darolutamide, similar to abiraterone, is limited by inevitable acquired resistance. Genomic aberrations that confer resistance to SG-ARAs or provide potential alternative treatment modalities have been identified in numerous studies, including alterations of the androgen receptor, DNA repair, cell cycle, PI3K-AKT-mTOR and Wnt-β-catenin pathways. To combat resistance, researchers have explored approaches to optimizing the utility of available treatments, as well as the use of alternative agents with a variety of targets, including AR-V7, AKT, EZH2 and HIF1α. Ongoing research to establish predictive biomarkers for the treatment of tumours with resistance to SG-ARAs led to the approval of the PARP inhibitors olaparib and rucaparib in pre-treated metastatic castration-resistant prostate cancer. The results of ongoing studies will help to shape precision medicine in prostate cancer and further optimize treatment paradigms to maximize clinical outcomes.read more
Citations
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Journal ArticleDOI
Tumor microenvironment heterogeneity an important mediator of prostate cancer progression and therapeutic resistance
TL;DR: In this article , the authors discuss how nongenetic factors contribute to heterogeneity of prostate cancer and summarize the challenges targeting the tumor environments, and emphasize that continued exploration of tumor heterogeneity is needed in order to offer a personalized therapy for advanced prostate cancer patients.
Journal ArticleDOI
Second generation androgen receptor antagonists and challenges in prostate cancer treatment
TL;DR: In this paper , the authors summarize the current state of AR antagonist development and highlight the emerging challenges of their clinical application and the potential resistance mechanisms, which might be addressed by combination therapies or the development of novel AR-targeted therapies.
Journal ArticleDOI
Immune system and intestinal microbiota determine efficacy of androgen deprivation therapy against prostate cancer
Safae Terrisse,Anne-Gaëlle Goubet,Kousuke Ueda,Andrew Maltez Thomas,Valentin Quiniou,Cassandra Thelemaque,Garett Dunsmore,Emmanuel Clave,Melissa Gamat-Huber,Satoru Yonekura,Gladys Ferrere,Conrad Rauber,Hang-Phuong Pham,Jean-Eudes Fahrner,Eugenie Pizzato,Pierre Ly,Marine Fidelle,Marine Mazzenga,Carolina Alves Costa Silva,Federica Armanini,Federica Pinto,Francesco Asnicar,Romain Daillère,Lisa Derosa,Corentin Richard,Pierre Blanchard,Bertrand Routy,Stéphane Culine,Paule Opolon,Aymeric Silvin,Florent Ginhoux,Antoine Toubert,Nicola Segata,Douglas G. McNeel,Karim Fizazi,Guido Kroemer,Laurence Zitvogel +36 more
TL;DR: The potential clinical utility of reversing intestinal dysbiosis and repairing acquired immune defects in PC patients is suggested, as compared with HSPC controls, CRPC patients demonstrated a shift in their intestinal microbiota that significantly correlated with sjTRECs.
Journal ArticleDOI
Unravelling the molecular mechanisms of prostate cancer evolution from genotype to phenotype.
TL;DR: The identification of canonical genetic alterations and signaling pathway activation in prostate cancer has shed more insight into genetic background, molecular subtype and disease landscape of PC evolution, resulting in a more flexible role of individual therapies targeting diverse genotype and phenotype presentation as discussed by the authors.
Journal ArticleDOI
Dissecting the Hormonal Signaling Landscape in Castration-Resistant Prostate Cancer.
TL;DR: In this paper, the role of the androgen/androgen receptor (AR) axis in prostate cancer (PCa) progression towards its most aggressive, castration-resistant (CRPC) stage is analyzed.
References
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Journal ArticleDOI
Mechanisms of Therapeutic Resistance in Prostate Cancer
TL;DR: The current understanding of mechanisms of therapeutic resistance in progression to and after the development of castration resistance is outlined, highlighting targetable and reversible mechanisms of resistance.
Journal ArticleDOI
Genomic Drivers of Poor Prognosis and Enzalutamide Resistance in Metastatic Castration-resistant Prostate Cancer.
William S. Chen,William S. Chen,Rahul Aggarwal,Li Zhang,Shuang G. Zhao,George Thomas,Tomasz M. Beer,David A. Quigley,Adam Foye,Denise Playdle,Jiaoti Huang,Paul Lloyd,Eric Lu,Duanchen Sun,Xiangnan Guan,Matthew Rettig,Matthew Rettig,Martin E. Gleave,Christopher P. Evans,Jack F. Youngren,Lawrence D. True,Primo N. Lara,Vishal Kothari,Zheng Xia,Kim N. Chi,Robert E. Reiter,Christopher G. Maher,Felix Y. Feng,Eric J. Small,Joshi J. Alumkal +29 more
TL;DR: Using whole-genome sequencing to assess the association between key driver gene alterations and overall survival (OS) and whole-transcriptome RNA sequencing to identify genomic drivers of enzalutamide resistance sheds new light on clinically relevant genomic alterations in mCRPC and provides a roadmap for the development of new personalized treatment regimens in m CRPC.
Journal ArticleDOI
High Efficacy of Combination Therapy Using PI3K/AKT Inhibitors with Androgen Deprivation in Prostate Cancer Preclinical Models
Rute B. Marques,Ashraf Aghai,Corrina M.A. de Ridder,Debra Stuurman,Sander Hoeben,Agnes Boer,Rebecca Ellston,Simon T. Barry,Barry R. Davies,Jan Trapman,Wytske M. van Weerden +10 more
TL;DR: Combination with hormonal therapy improved efficacy of PI3K/AKT-targeted agents in PTEN-negative PCa models and resulted in long-lasting tumor regression, which persisted after treatment cessation.
Journal ArticleDOI
Targeting FOXA1-mediated repression of TGF-β signaling suppresses castration-resistant prostate cancer progression
Bing Song,Su-Hong Park,Jonathan C. Zhao,Ka Wing Fong,Shangze Li,Yongik Lee,Yeqing A. Yang,Subhasree Sridhar,Xiaodong Lu,Sarki A. Abdulkadir,Robert L. Vessella,Colm Morrissey,Timothy M. Kuzel,William J. Catalona,Ximing J. Yang,Jindan Yu +15 more
TL;DR: This study establishes FOXA1 as an important regulator of lineage plasticity mediated in part by TGF-&bgr; signaling, and supports a novel therapeutic strategy to control lineage switching and potentially extend clinical response to antiandrogen therapies.
Journal ArticleDOI
Approval Summary Docetaxel in Combination with Prednisone for the Treatment of Androgen-Independent Hormone-Refractory Prostate Cancer
TL;DR: The Food and Drug Administration review supporting this first approval of a combination therapy for hormone-refractory prostate cancer based on demonstration of a survival benefit is described.