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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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
Genomic Analysis of Three Metastatic Prostate Cancer Patients with Exceptional Responses to Carboplatin Indicating Different Types of DNA Repair Deficiency.
Zafeiris Zafeiriou,Diletta Bianchini,Robert Chandler,Pasquale Rescigno,Wei Yuan,Suzanne Carreira,Maialen Barrero,Antonella Petremolo,Susana Miranda,Ruth Riisnaes,Daniel Nava Rodrigues,Bora Gurel,Semini Sumanasuriya,Alec Paschalis,Adam Sharp,Joaquin Mateo,Nina Tunariu,Arul M. Chinnaiyan,Colin C. Pritchard,Kevin Kelly,Johann S. de Bono +20 more
TL;DR: Three patients with advanced castration-resistant PCa with HRD defects having exceptional responses to carboplatin are reported.
Journal ArticleDOI
N-Myc promotes therapeutic resistance development of neuroendocrine prostate cancer by differentially regulating miR-421/ATM pathway
Yu Yin,Yu Yin,Lingfan Xu,Lingfan Xu,Yan Chang,Yan Chang,Tao Zeng,Xufeng Chen,Aifeng Wang,Jeff Groth,Wen-Chi Foo,Chaozhao Liang,Hailiang Hu,Hailiang Hu,Jiaoti Huang,Jiaoti Huang +15 more
TL;DR: Surprisingly, N-Myc overexpression upregulated ATM expression in C4–2 cells and this upregulation promoted migration and invasion of prostate cancer cells and N- myc differentially regulating miR-421/ATM pathway contributes to ADT resistance and Enzalutamide resistance development respectively.
Journal ArticleDOI
Enzalutamide-resistant castration-resistant prostate cancer: challenges and solutions.
Marcello Tucci,Clizia Zichi,Consuelo Buttigliero,Francesca Vignani,Giorgio V. Scagliotti,Massimo Di Maio +5 more
TL;DR: This review focuses on resistance mechanisms to enzalutamide, exploring how to overcome them through novel therapeutic options.
Journal ArticleDOI
Significance of the TMPRSS2:ERG gene fusion in prostate cancer.
Zhu Wang,Yuliang Wang,Jianwen Zhang,Qiyi Hu,Fan Zhi,Shengping Zhang,Dengqi Mao,Ying Zhang,Hui Liang +8 more
TL;DR: Target inhibition of ERG expression could significantly cause cell growth arrest in prostate cancer cells, which could be a potentially valuable target for prostate cancer treatment, although the precise mechanism of these results remains unclear.
Journal ArticleDOI
Whole Genomic Copy Number Alterations in Circulating Tumor Cells from Men with Abiraterone or Enzalutamide-Resistant Metastatic Castration-Resistant Prostate Cancer.
Santosh Gupta,Jing Li,Gabor Kemeny,Rhonda L. Bitting,Joshua Beaver,Jason A. Somarelli,Kathryn E. Ware,Simon G. Gregory,Andrew J. Armstrong +8 more
TL;DR: Genomic analysis of pooled CTCs in men with mCRPC suggests a reproducible, but highly complex molecular profile that includes common aberrations in AR, ERG, c-MET, and PI3K signaling during m CRPC progression, which may be useful for predictive biomarker development.