Article
Cell Biology
Xiao Li, Fei Li, Fei Ye, Haotian Guo, Wentao Chen, Jia Jin, Yiran Wang, Pengfei Dai, Huili Shi, Hongru Tao, Wenzhen Dang, Yiluan Ding, Mingchen Wang, Hualiang Jiang, Kaixian Chen, Naixia Zhang, Dong Gao, Yuanyuan Zhang, Cheng Luo
Summary: In castration-resistant prostate cancer (CRPC), the limited response to androgen receptor (AR) antagonists is mainly attributed to the expression of AR-variants and restored AR signaling. We demonstrate that the metabolite spermine inhibits AR-FL and AR-V7 signaling and suppresses CRPC cell proliferation by directly binding and inhibiting PRMT1. Additionally, spermine supplementation restrains CRPC growth in vivo. Thus, spermine and PRMT1 inhibition may be powerful strategies for overcoming the limitations of current AR-based therapies in CRPC.
Article
Oncology
Emuejevoke Olokpa, Sammed N. Mandape, Siddharth Pratap, La Monica Stewart
Summary: The study used RNA sequencing to identify the signaling pathways regulated by metformin in androgen-receptor positive, castration-resistant prostate cancer cells. Metformin was found to alter the expression of genes involved in metabolic pathways, the spliceosome, RNA transport, and protein processing within the endoplasmic reticulum, as well as in ErbB, insulin, mTOR, TGF-beta, MAPK, and Wnt signaling pathways. Some of the metformin-regulated genes are known to be direct transcriptional targets of p53 or AR, and metformin-induced reductions in AR mRNA and protein levels contributed to these alterations in gene expression.
Article
Oncology
Fen Ma, Seiji Arai, Keshan Wang, Carla Calagua, Amanda R. Yuan, Larysa Poluben, Zhongkai Gu, Joshua W. Russo, David J. Einstein, Huihui Ye, Meng Xiao He, Yu Liu, Eliezer Van Allen, Adam G. Sowalsky, Manoj K. Bhasin, Xin Yuan, Steven P. Balk
Summary: This study reveals the importance of Wnt/beta-catenin signaling in prostate cancer, showing its role in stem cell maintenance and invasion. It identifies new effectors and drivers of this pathway in prostate cancer, such as ROR1 and APC genomic loss. The findings suggest that targeting Wnt/beta-catenin signaling may be a potential therapeutic strategy for prostate cancer.
Article
Cell Biology
Tianyan Wang, Martuza Sarwar, Jonathan B. Whitchurch, Hilary M. Collins, Tami Green, Julius Semenas, Amjad Ali, Christopher J. Roberts, Ryan D. Morris, Madlen Hubert, Sa Chen, Zahra El-Schich, Anette G. Wingren, Thomas Grundstroem, Richard Lundmark, Nigel P. Mongan, Lena Gunhaga, David M. Heery, Jenny L. Persson
Summary: This study identifies the role of PIP5K1α in promoting the growth and invasion of castration-resistant prostate cancer. The study also reveals the importance of the N-terminal domain of PIP5K1α and its function as an upstream regulator of androgen receptor and its target genes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Fabrizio Fontana, Patrizia Limonta
Summary: Understanding the molecular mechanisms of prostate cancer progression to the castration-resistant stage is crucial for improving therapeutic options. The activation of the androgen/androgen receptor axis and the GnRH/GnRH-R axis in CRPC cells play significant roles in antitumor activity, suggesting potential therapeutic implications.
Review
Biochemistry & Molecular Biology
Stephen Y. C. Choi, Caroline Fidalgo Ribeiro, Yuzhuo Wang, Massimo Loda, Stephen R. Plymate, Takuma Uo
Summary: This article discusses the urgent need to explore new actionable targets other than the androgen receptor to improve treatment outcomes for castration-resistant prostate cancer. Tumor metabolism is considered a hallmark of cancer and understanding its relationship with androgen receptor signaling, genetic drivers, and the tumor microenvironment is important for identifying metabolic vulnerabilities. The article also provides an overview of current metabolism-based pharmacological strategies for treating castration-resistant prostate cancer.
Review
Biochemistry & Molecular Biology
David Ka-Wai Leung, Peter Ka-Fung Chiu, Chi-Fai Ng, Jeremy Yuen-Chun Teoh
Summary: The management of castration-resistant prostate cancer has seen significant progress, with three novel hormonal agents showing survival benefits in non-metastatic patients and a wider range of management options being investigated for metastatic disease.
Review
Medicine, General & Internal
Tianyi Zhou, Qin Feng
Summary: Prostate cancer is a major cause of cancer death, affecting millions of men worldwide. The progression to castration-resistant prostate cancer (CRPC) is associated with dependence on androgen receptor (AR) signaling, which involves various transcription factors. Understanding the role of transcription factors in CRPC could lead to new therapeutic targets for treatment.
FRONTIERS IN MEDICINE
(2022)
Article
Oncology
Maryam Labaf, Muqing Li, Lily Ting, Breelyn Karno, Songqi Zhang, Shuai Gao, Susan Patalano, Jill A. A. Macoska, Kourosh Zarringhalam, Dong Han, Changmeng Cai
Summary: This study examines the acute effects of overexpressed androgen receptor (AR) on its cistrome and transcriptome in a prostate cancer (PCa) model. The results show that overexpression of AR leads to redistribution of AR chromatin binding and activation of a distinct transcription program, including DNA damage repair pathways. The study also predicts the involvement of EZH2 in this AR reprogramming and identifies a subset of AR/EZH2 co-targeting genes that are overexpressed in castration-resistant PCa and associated with worse patient outcomes.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Wei -Yu Chen, Phan Vu Thuy Dung, Hsiu-Lien Yeh, Wei-Hao Chen, Kuo-Ching Jiang, Han-Ru Li, Zi-Qing Chen, Michael Hsiao, Jiaoti Huang, Yu-Ching Wen, Yen-Nien Liu
Summary: The conventional treatment for prostate cancer is androgen-deprivation therapy (ADT), which inhibits tumor progression driven by androgen receptor (AR) signaling. ADT-induced recurrence of prostate cancer can develop into a neuroendocrine (NE) phenotype with metabolic disturbances and poor prognosis. However, the metabolic pathways that regulate NE differentiation (NED) in prostate cancer are still unclear.
Article
Oncology
Lin Gao, Ru Zhao, Junmei Liu, Wenbo Zhang, Feifei Sun, Qianshuo Yin, Xin Wang, Meng Wang, Tingting Feng, Yiming Qin, Wenjie Cai, Qianni Li, Hanchen Dong, Xueqing Chen, Xueting Xiong, Hui Liu, Jing Hu, Weiwen Chen, Bo Han
Summary: KIF15 overexpression in CRPC is associated with enhanced EGFR signaling, linking it to disease progression and suggesting KIF15 as a potential therapeutic target.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Serina Cheung, Pallavi Jain, Jonathan So, Saeid Shahidi, Stephen Chung, Marianne Koritzinsky
Summary: Targeting the p38 MAPK protein kinase can inhibit growth and survival of castration-resistant prostate cancer cells, regardless of oxygen levels, and may prolong the survival of tumor-bearing mice. This demonstrates the potential of p38 MAPK inhibition as a therapeutic strategy for disrupting AR signaling in the heterogeneous CRPC tumor microenvironment.
Article
Pharmacology & Pharmacy
Lang Guo, Xiaowei Luo, Ping Yang, Yanting Zhang, Jialuo Huang, Hong Wang, Yinfeng Guo, Weifeng Huang, Zhiqiang Chen, Shusheng Wang, Junjian Wang, Jinping Lei, Songtao Xiang, Yonghong Liu
Summary: The Polycomb protein enhancer EZH2 plays a critical role in prostate cancer progression and drug resistance, making it a major obstacle in treatment. Enzalutamide is a common drug used for metastatic castration-resistant prostate cancer, but many tumors eventually develop resistance to it. Ilicicolin A (Ili-A) has shown potential to overcome resistance and enhance the anticancer activity of enzalutamide in CRPC cancer models.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Engineering, Biomedical
Nicole L. Habbit, Benjamin Anbiah, Joshita Suresh, Luke Anderson, Megan L. Davies, Iman Hassani, Taraswi M. Ghosh, Michael W. Greene, Balabhaskar Prabhakarpandian, Robert D. Arnold, Elizabeth A. Lipke
Summary: Using a 3D-engineered prostate cancer (PCa) tissue model, this study reveals that the incorporation of fibroblasts promotes PCa aggression by increasing proliferation, significant matrix remodeling, and enrichment of tumorigenic hallmark gene sets. Fibroblasts play an elevated role in indolent disease states and may contribute to the switch from androgen-dependent to castration-resistant PCa.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Cell & Tissue Engineering
Yalan Xu, Jie Mu, Zhixia Zhou, Yu Leng, Yali Yu, Xiuyue Song, Aihua Liu, Hai Zhu, Jing Li, Dong Wang
Summary: The study isolated and cultured a novel type of castration-resistant intermediate prostate stem cells that can rapidly proliferate in 2D culture dishes and be maintained for over six months. These stem cells express markers of both basal and luminal cells, and can differentiate into prostate organoids and tissues.
STEM CELL RESEARCH & THERAPY
(2022)