Review
Oncology
Zeyuan Zheng, Jinxin Li, Yankuo Liu, Zhiyuan Shi, Zuodong Xuan, Kunao Yang, Chunlan Xu, Yang Bai, Meiling Fu, Qiaohong Xiao, Huimin Sun, Chen Shao
Summary: This review summarizes the mechanisms and biological behaviors of AR-V7 in enzalutamide resistance of castration-resistant prostate cancer (CRPC), providing novel insights for CRPC therapy.
Article
Biology
Meng Wu, Rongyu Zhang, Zixiong Zhang, Ning Zhang, Chenfan Li, Yongli Xie, Haoran Xia, Fangjiao Huang, Ruoying Zhang, Ming Liu, Xiaoyu Li, Shan Cen, Jinming Zhou
Summary: A bifunctional small molecule called Z15 was discovered and identified as an effective and selective androgen receptor (AR) antagonist and degrader. It interacts with the ligand-binding domain (LBD) and activation function-1 region of AR, promoting its degradation through the proteasome pathway. In vitro and in vivo studies showed that Z15 successfully suppressed AR, AR mutants, and AR splice variants (ARVs) transcription activity, overcoming resistance to second-generation antiandrogens (SGAs) induced by AR LBD mutations, amplification, and ARVs. This highlights the synergistic importance of AR antagonism and degradation in advanced prostate cancer treatment.
Article
Biochemistry & Molecular Biology
Eunjeong Seo, Byula Jee, Jae Hoon Chung, Wan Song, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Minyong Kang
Summary: In this study, the researchers discovered that the AR-V7/YAP1/TAZ axis represses the expression of SLC22A3, leading to resistance to enzalutamide (ENZ) in metastatic castration-resistant prostate cancer (mCRPC). This finding provides new insights into potential treatment targets for prostate cancer.
Article
Oncology
Masahiro Sugiura, Hiroaki Sato, Atsushi Okabe, Masaki Fukuyo, Yasunobu Mano, Ken-ichi Shinohara, Bahityar Rahmutulla, Kosuke Higuchi, Maihulan Maimaiti, Manato Kanesaka, Yusuke Imamura, Tomomi Furihata, Shinichi Sakamoto, Akira Komiya, Naohiko Anzai, Yoshikatsu Kanai, Jun Luo, Tomohiko Ichikawa, Atsushi Kaneda
Summary: The study found that AR-V7 contributes to the proliferation of CRPC by activating both common AR/AR-V7 target genes and specific AR-V7 target genes, such as NUP210 and SLC3A2. These findings suggest that targeting NUP210 and SLC3A2 may be a potential therapeutic strategy for CRPC.
TRANSLATIONAL ONCOLOGY
(2021)
Article
Oncology
Dali Tong
Summary: Castration-resistant prostate cancer (CRPC) is still a bottleneck in prostate cancer research and treatment, with abnormal androgen receptor (AR) activation playing a crucial role. The production of overabundant AR-V7 mRNA splicing is currently a focus of study, but there is no definite conclusion about its regulation. Recent research has shown that JMJD6 and U2AF65 may be a promising approach in mRNA splicing regulation.
CANCER CELL INTERNATIONAL
(2021)
Article
Oncology
Lin Gao, Wenbo Zhang, Jing Zhang, Junmei Liu, Feifei Sun, Hui Liu, Jing Hu, Xin Wang, Xueli Wang, Peng Su, Shouzhen Chen, Sifeng Qu, Benkang Shi, Xueting Xiong, Weiwen Chen, Xuesen Dong, Bo Han
Summary: The study reveals that KIF15 contributes to enzalutamide resistance by enhancing AR signaling, and suggests that cotargeting KIF15 and AR may be an effective therapeutic strategy for prostate cancer.
Article
Cell Biology
Boya Zhang, Mingpeng Zhang, Chunyi Shen, Guancong Liu, Fan Zhang, Jingyu Hou, Weitao Yao
Summary: The study revealed the key role of LncRNA PCBP1-AS1 in drug resistance of castration-resistant prostate cancer, by stabilizing the AR/AR-V7 complex to prevent degradation. Targeting PCBP1-AS1 can significantly restore drug sensitivity in resistant tumors.
CELL DEATH & DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Navid Sobhani, Praveen Kumar Neeli, Alberto D'Angelo, Matteo Pittacolo, Marianna Sirico, Ilaria Camilla Galli, Giandomenico Roviello, Gabriella Nesi
Summary: Metastatic prostate cancer is the most common cancer in males with a poor prognosis, and many patients develop the AR-V7 variant. AR-V7 acts as a transcription factor in the nucleus, repressing crucial tumor suppressor genes. Anti-AR-V7 drugs show promise for this subset of patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Zhengfang Liu, Cheng Liu, Keqiang Yan, Jikai Liu, Zhiqing Fang, Yidong Fan
Summary: The huaier extract demonstrated potent antiproliferative effects in both hormone sensitive prostate cancer (HSPC) and castration-resistant prostate cancer (CRPC) cells by downregulating AR-FL and AR-V7 mRNA levels via targeting the SMYD3 signaling pathway, and enhancing proteasome-mediated protein degradation of AR-FL and AR-V7 by downregulating USP14. Additionally, the extract inhibited AR transcriptional activity and their nuclear translocation, and could re-sensitize enzalutamide-resistant prostate cancer cells to enzalutamide treatment in vitro and in vivo models.
FRONTIERS IN ONCOLOGY
(2021)
Review
Pharmacology & Pharmacy
Yuanyuan Wang, Jiyuan Chen, Zhengjie Wu, Weihong Ding, Shen Gao, Yuan Gao, Chuanliang Xu
Summary: This review examines the emerging information on resistance mechanisms to enzalutamide in castration-resistant prostate cancer, including various signaling pathways and metabolic effects, and suggests potential therapeutic strategies for overcoming enzalutamide resistance.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Katrin Schlack, Konstantin Seitzer, Neele Wuestmann, Verena Humberg, Norbert Grundmann, Julie Steinestel, Dorothee Tiedje, Kambiz Rahbar, Laura-Maria Krabbe, Martin Boegemann, Andres J. Schrader, Christof Bernemann
Summary: This study aimed to compare the clinical value of circulating tumor cells (CTCs) and androgen receptor splice variant 7 (AR-V7) as biomarkers in mCRPC patients. The study found that both biomarkers have clinical value in predicting clinical outcomes, but the stratification of AR-V7 may underestimate CTC-negative patients and AR-V7 level does not correlate with clinical response.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Manjul Rana, Jianrong Dong, Matthew J. Robertson, Cristian Coarfa, Nancy L. Weigel
Summary: This study found differences in transcription and splicing regulation between AR-V7 and AR in prostate cancer, leading to the generation of different gene products.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Khrystany T. Isebia, Bianca Mostert, Bodine P. S. Belderbos, Stefan A. J. Buck, Jean C. A. Helmijr, Jaco Kraan, Corine M. Beaufort, Mai N. Van, Esther Oomen-de Hoop, Anieta M. Sieuwerts, Wilfred F. J. van IJcken, Mirjam C. G. N. van den Hout van Vroonhoven, Rutger W. W. Brouwer, Edwin Oole, Paul Hamberg, Brigitte C. M. Haberkorn, Helgi H. Helgason, Ronald de Wit, Stefan Sleijfer, Ron H. J. Mathijssen, John W. M. Martens, Maurice P. H. M. Jansen, Job van Riet, Martijn P. Lolkema
Summary: This study aimed to investigate the clinical efficacy of cabazitaxel treatment in AR-V7 positive mCRPC patients and collect liquid biopsy samples for genomic profiling.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Oncology
Alec Paschalis, Jonathan Welti, Antje J. Neeb, Wei Yuan, Ines Figueiredo, Rita Pereira, Ana Ferreira, Ruth Riisnaes, Daniel Nava Rodrigues, Juan M. Jimenez-Vacas, Soojin Kim, Takuma Uo, Patrizio Di Micco, Anthony Tumber, Md Saiful Islam, Marc A. Moesser, Martine Abboud, Akane Kawamura, Bora Gurel, Rossitza Christova, Veronica S. Gil, Lorenzo Buroni, Mateus Crespo, Susana Miranda, Maryou B. Lambros, Suzanne Carreira, Nina Tunariu, Andrea Alimonti, Bissan Al-Lazikani, Christopher J. Schofield, Stephen R. Plymate, Adam Sharp, Johann S. de Bono
Summary: This study identifies JMJD6 as critical for the generation of AR-V7 in prostate cancer, where it may serve as a tractable target for therapeutic intervention.
Article
Cell Biology
Haojie Chen, Jia Luo, Shaojun Chen, Bowen Shi, Xiaocui Zheng, Haiying Ji, Xiaoqian Zhang, Yujia Yin, Kun Du, Jie Ding, Yongjiang Yu
Summary: ABCC5 may serve as a novel target for enzalutamide-resistant CRPC treatment by affecting resistance to enzalutamide through its non-drug efflux function.
CELL DEATH DISCOVERY
(2022)
Article
Pharmacology & Pharmacy
Yuan Liu, Zhenlong Shao, Yuning Liao, Xiaohong Xia, Chuyi Huang, Jinchan He, Tumei Hu, Cuifu Yu, Lili Jiang, Jinbao Liu, Hongbiao Huang
EUROPEAN JOURNAL OF PHARMACOLOGY
(2020)
Article
Oncology
Yuning Liao, Zhenlong Shao, Yuan Liu, Xiaohong Xia, Yuanfei Deng, Cuifu Yu, Wenshuang Sun, Weiyao Kong, Xiaoyue He, Fang Liu, Zhiqiang Guo, Guoxing Chen, Daolin Tang, Huoye Gan, Jinbao Liu, Hongbiao Huang
Summary: The activation of the USP1-RPS16 pathway plays an unrecognized role in driving HCC, which may be developed as a novel strategy for cancer treatment.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Yuning Liao, Yuan Liu, Zhenlong Shao, Xiaohong Xia, Yuanfei Deng, Jianyu Cai, Leyi Yao, Jinchan He, Cuifu Yu, Tumei Hu, Wenshuang Sun, Fang Liu, Daolin Tang, Jinbao Liu, Hongbiao Huang
Summary: The study revealed the key role of the molecular chaperone GRP75 in maintaining the protein stability of SIX1 in prostate cancer cells, inhibiting tumor growth and overcoming castration resistance by recruiting the deubiquitinating enzyme USP1 to inhibit polyubiquitination of SIX1. The expression of GRP75, USP1, and SIX1 proteins are positively correlated in clinical prostate cancer tissues.
Article
Biochemistry & Molecular Biology
Yuning Liao, Wenshuang Sun, Zhenlong Shao, Yuan Liu, Xiaoyu Zhong, Yuanfei Deng, Fang Liu, Hongbiao Huang, Jinbao Liu
Summary: The study aimed to identify a SIX1 degradation inducer through inhibiting the USP1-SIX1 axis, and found that SNS-032 is the best candidate. SNS-032 not only inhibits the activity of the USP1-SIX1 axis and cell cycle progression, but also induces apoptosis in prostate cancer cells.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)