Article
Cell Biology
Tingting Zhou, Shengli Wang, Xiaoyu Song, Wensu Liu, Fang Dong, Yunlong Huo, Renlong Zou, Chunyu Wang, Siyi Zhang, Wei Liu, Ge Sun, Lin Lin, Kai Zeng, Xiang Dong, Qiqiang Guo, Fei Yi, Zhuo Wang, Xiaoman Li, Bo Jiang, Liu Cao, Yue Zhao
Summary: The study reveals the potential function of RNF8 in prostate cancer progression and its correlation with poor prognosis. RNF8 regulates prostate cancer development by altering histone modifications and promoting AR transcriptional activity and recruitment. RNF8 may serve as a potential therapeutic target for endocrine-resistant prostate cancer.
CELL DEATH & DISEASE
(2022)
Article
Pharmacology & Pharmacy
Yan Li, Ya Chu, Guangjiang Shi, Xiaobin Wang, Wanli Ye, Chun Shan, Dajia Wang, Di Zhang, Wei He, Jingwei Jiang, Shuqian Ma, Yuhong Han, Zhili Zhao, Shijia Du, Zhen Chen, Zhiyu Li, Yong Yang, Chen Wang, Xi Xu, Hongxi Wu
Summary: The small molecule LLU-206, designed based on the structure of Enzalutamide, has been found to effectively inhibit prostate cancer cell proliferation and resistance. LLU-206 promotes protein degradation and reduces heterodimers formation of AR. Compared to Enzalutamide, LLU-206 has better pharmacokinetic properties and lower occurrence of adverse effects.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Oncology
Yara Rodriguez, Kenji Unno, Mihai I. Truica, Zachary R. Chalmers, Young A. Yoo, Rajita Vatapalli, Vinay Sagar, Jindan Yu, Barbara Lysy, Maha Hussain, Huiying Han, Sarki A. Abdulkadir
Summary: This study identifies PRRX2 as a driver of enzalutamide resistance in prostate cancer. PRRX2 expression is highest in double-negative prostate cancer cases and its associated gene signature can serve as a biomarker for enzalutamide resistance, which can be reversed with CDK4/6 and BCL2 inhibitors.
Article
Materials Science, Biomaterials
Ze Gao, Jun Huang, Zhaoxiang Xie, Peikun Xin, Hao Huang, Tao Du, Jun Wu, Hai Huang
Summary: This article proposes a strategy of using a biocompatible nanoparticle drug delivery system to improve the bioavailability and therapeutic performance of enzalutamide. The system has been shown to enhance drug delivery efficiency, increase drug cytotoxicity, and reduce the half-inhibitory concentration of the drug, thus demonstrating great potential for the treatment of prostate cancer.
BIOMATERIALS SCIENCE
(2022)
Article
Oncology
Ke Gao, Xiaoshun Li, Jianxin Ni, Bin Wu, Jiaheng Guo, Rui Zhang, Guojun Wu
Summary: This article introduces the roles of dysregulation of different subclasses of non-coding RNAs (ncRNAs) in the development of castration-resistant prostate cancer (CRPC) progression and Enzalutamide (Enz) resistance. The mechanisms of Enz resistance, including AR-splice variant-7 (AR-V7), mutations, circRNAs, and lncRNAs that act as miRNA sponges, are discussed. The contributions of epithelial-mesenchymal transition and glucose metabolism to Enz resistance are also highlighted. The article summarizes the different mechanisms of miRNAs, lncRNAs, and circRNAs in the progression of CRPC and Enz resistance, and discusses future therapeutic strategies against Enz resistance.
Article
Oncology
Petra Deegen, Oliver Thomas, Olivier Nolan-Stevaux, Shyun Li, Joachim Wahl, Pamela Bogner, Famke Aeffner, Matthias Friedrich, Michael Z. Liao, Katja Matthes, Doris Rau, Benno Rattel, Tobias Raum, Peter Kufer, Angela Coxon, Julie M. Bailis
Summary: AMG 160, a bispecific T-cell engager immuno-oncology therapy targeting PSMA in mCRPC, demonstrates potent antitumor activity in vitro and in vivo. It shows enhanced cytotoxic activity when combined with diagnostic or therapeutic agents such as the PSMA-imaging agent, novel hormonal therapy, and immune checkpoint blockade. Preclinical data supports ongoing clinical evaluation in patients with mCRPC.
CLINICAL CANCER RESEARCH
(2021)
Article
Chemistry, Medicinal
Sergey A. Dyshlovoy, Olesya I. Zhuravleva, Jessica Hauschild, Tobias Busenbender, Dmitry N. Pelageev, Anton N. Yurchenko, Yuliya V. Khudyakova, Alexandr S. Antonov, Markus Graefen, Carsten Bokemeyer, Gunhild von Amsberg
Summary: Marine fungi are a valuable source for new bioactive molecules with various biological activities. In this study, a new indole diketopiperazine alkaloid, deoxy-14,15-dehydroisoaustamide (1), was isolated from the marine-derived fungus Penicillium dimorphosporum KMM 4689 associated with a soft coral. The structure and absolute configuration of this metabolite were determined using HR-MS, 1D and 2D NMR, and CD data. Compound 1 showed no cytotoxicity against human normal and cancer cell lines up to 100 μM, but it resensitized prostate cancer 22Rv1 cells to the androgen receptor (AR) blocker enzalutamide by inducing degradation of the AR transcription variant V7 (AR-V7) and suppressing AR signaling. This isolated alkaloid holds promise as a candidate for combinational therapy of castration resistant prostate cancer, including drug-resistant subtypes.
Article
Cell Biology
Haleema Azam, Shane Maher, Shane Clarke, William M. Gallagher, Maria Prencipe
Summary: Inhibition of androgen receptor (AR) co-factor SRF provides a promising approach for overcoming resistance to current AR inhibitors in prostate cancer. Three small molecules (CCG-1423, CCG-257081, and lestaurtinib) can effectively reduce cell viability and induce cell cycle arrest and decreased proliferation, either singly or in combination with enzalutamide.
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.
Review
Biochemistry & Molecular Biology
Demitria M. Vasilatis, Christopher A. Lucchesi, Paramita M. Ghosh
Summary: Dogs naturally develop prostate cancer similar to aggressive forms found in humans. Prostate cancer samples in dogs often lack androgen receptor (AR), which can enhance our understanding of AR-indifferent prostate cancer in humans. This review highlights the molecular similarities between dog and human prostate cancer variants, suggesting the potential use of dogs as pre-clinical animal models for developing new therapies and diagnostics that can benefit both species.
Article
Oncology
Seiji Hoshi, Satoru Meguro, Hitomi Imai, Yuta Matsuoka, Yuki Yoshida, Akihumi Onagi, Ryo Tanji, Ruriko Honda-Takinami, Kanako Matsuoka, Tomoyuki Koguchi, Junya Hata, Yuichi Sato, Hidenori Akaihata, Masao Kataoka, Soichiro Ogawa, Yoshiyuki Kojima
Summary: Enzalutamide prolongs survival time in castration-resistant prostate cancer patients, but resistance to Enz and other AR signaling inhibitors is common during treatment. Chronic Enz treatment induces GR-mediated GLUT4 upregulation, which is associated with resistance and can be suppressed to inhibit cell proliferation in Enz-resistant prostate cancer cells.
Editorial Material
Cell Biology
Li Xin
Summary: EZH2 has been shown to promote the development of castration-resistant prostate cancer (CRPC) by interacting with the androgen receptor (AR) to reprogram its transcriptional activity, facilitating the transition of CRPC into a lineage infidelity state.
NATURE CELL BIOLOGY
(2021)
Article
Cell Biology
Jia Xia, Jiahui Zhang, Liangzhe Wang, Hailong Liu, Jie Wang, Junyan Liu, Zhaoqian Liu, Yingjian Zhu, Yingjie Xu, Wen Yang, Yongjiang Yu
Summary: Caspase-8 plays a dual role in cell death and survival in cancer, and its upregulation in enzalutamide-resistant prostate cancer leads to increased NF-kappa B/IL-8 mediated survival signaling, contributing to therapy resistance. Targeting Caspase-8 and NF-kappa B may be a potential strategy to overcome enzalutamide resistance in CRPC.
CELL DEATH & DISEASE
(2021)
Review
Oncology
Mathieu Roumiguie, Xavier Paoletti, Yann Neuzillet, Romain Mathieu, Sebastien Vincendeau, Francois Kleinclauss, Arnaud Mejean, Laurent Guy, Marc Olivier Timsit, Thierry Lebret
Summary: The study compared the efficacy, safety, and health-related quality of life of apalutamide, enzalutamide, and darolutamide in patients with nonmetastatic castration-resistant prostate cancer. Results showed that all three drugs significantly prolonged survival compared to placebo and were generally well tolerated. Therefore, drug selection in clinical practice should be based on individual patient factors such as tolerability, drug interactions, and comorbidities.
Article
Biochemistry & Molecular Biology
Eliot B. Blatt, Karla Parra, Antje Neeb, Lorenzo Buroni, Denisa Bogdan, Wei Yuan, Yunpeng Gao, Collin Gilbreath, Alec Paschalis, Suzanne Carreira, Ralph J. DeBerardinis, Ram S. Mani, Johann S. de Bono, Ganesh V. Raj
Summary: Therapy resistance to enzalutamide, a second-generation androgen receptor antagonist, is common in advanced prostate cancer (PCa) patients. This resistance is associated with higher levels of reactive oxygen species (ROS) and enhanced glutamine metabolism. Inhibiting glutamine metabolism or targeting antioxidant pathways can block the growth of enzalutamide-resistant PCa cells.
Article
Biochemistry & Molecular Biology
Hangchuan Shi, Yin Sun, Miao He, Xiong Yang, Michiaki Hamada, Tsukasa Fukunaga, Xiaoping Zhang, Chawnshang Chang
Article
Biochemistry & Molecular Biology
Jinbo Chen, Fuju Chou, Shuyuan Yeh, Zhenyu Ou, Chihrong Shyr, Chiping Huang, Zhendong Xiang, Yin Sun, Edward Messing, Xiongbing Zu, Chawnshang Chang
Article
Cell Biology
Bianjiang Liu, Yin Sun, Min Tang, Chao Liang, Chi-Ping Huang, Yuanjie Niu, Zengjun Wang, Chawnshang Chang
CELL DEATH & DISEASE
(2020)
Article
Oncology
Hao Tian, Fu-ju Chou, Jing Tian, Yong Zhang, Bosen You, Chi-Ping Huang, Shuyuan Yeh, Yuanjie Niu, Chawnshang Chang
Summary: ASC-J9 (R) can suppress prostate cancer progression via an androgen receptor-independent mechanism by altering ATF3 expression, leading to decreased PTK2 expression. Clinical and preclinical studies support the role of ATF3/PTK2 signaling in PCa progression.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Cell Biology
Zhendong Xiang, Yin Sun, Bosen You, Meng Zhang, Chiping Huang, Junfeng Yu, Xiangyun You, Denglong Wu, Chawnshang Chang
Summary: The study found that Enzalutamide-resistant prostate cancer cells can be suppressed by high doses of the androgen DHT. Targeting the BCL-XL protein can enhance the inhibitory effect of high-dose DHT on cell growth, promoting cell death.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Bosen You, Yin Sun, Jie Luo, Keliang Wang, Qing Liu, Ruizhe Fang, Bingmei Liu, Fuju Chou, Ronghao Wang, Jialin Meng, Chi-Ping Huang, Shuyuan Yeh, Chawnshang Chang, Wanhai Xu
Summary: The study suggests that androgen receptor (AR) promotes vasculogenic mimicry (VM) formation in ccRCC cells by regulating lncRNA-TANAR/TWIST1 signals, potentially impacting metastasis. This discovery provides a clue for the development of a novel anti-angiogenesis therapy to better suppress ccRCC progression.
Article
Oncology
Dongkui Gong, Yin Sun, Changcheng Guo, Tzong-jen Sheu, Wei Zhai, Junhua Zheng, Chawnshang Chang
Summary: The study revealed gender differences in RBM, with higher AR expression potentially linked to fewer RBMs by suppressing osteolytic formation. Mechanism dissection showed that AR can decrease circEXOC7 expression by enhancing transcription of DHX9, leading to suppression of CSF1 expression. Results from clinical epidemiological surveys found positive correlation between AR and miR-149-3p, and negative correlation between AR and CSF1 in AR-positive ccRCC tissues.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Gang Deng, Ronghao Wang, Yin Sun, Chi-Ping Huang, Shuyuan Yeh, Bosen You, Changyong Feng, Gonghui Li, Shenglin Ma, Chawnshang Chang
Summary: Targeting androgens/androgen receptor signals can affect the invasion capability of prostate cancer and bladder cancer cells, with prostate cancer cell invasion increasing while bladder cancer cell invasion decreasing. This difference may be due to the distinct alterations in selective circular RNAs resulting from differential endogenous AR transcription, along with differential histone H3K4 methylation patterns and binding of AR to different androgen-response elements.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Cell Biology
Meng Zhang, Yin Sun, Chi-Ping Huang, Jie Luo, Li Zhang, Jialin Meng, Chaozhao Liang, Chawnshang Chang
Summary: The study identified that lnc-OPHN1-5 plays a role in increasing prostate cancer sensitivity to Enzalutamide by regulating AR protein expression. The mechanism involves lnc-OPHN1-5 interacting with AR-mRNA to influence ribosome association and translation by modulating hnRNPA1.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Kuo-Chung Lan, Kuo-Ting Wei, Pei-Wen Lin, Ching-Chen Lin, Pei-Ling Won, Ya-Fen Liu, Yun-Ju Chen, Bi-Hua Cheng, Tien-Min G. Chu, Jia-Feng Chen, Ko-En Huang, Chawnshang Chang, Hong-Yo Kang
Summary: The study found that androgen receptor (AR) is highly expressed in periosteum cells during bone fracture repair and is co-localized with a mesenchymal progenitor cell marker, Prrx1. Mice lacking AR in periosteum showed reduced callus size and new bone volume. Targeting the androgen/AR axis in periosteum may provide a novel therapy approach to improve fracture healing.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Jie Ding, Xin-Gang Cui, Hao-Jie Chen, Yin Sun, Wei-Wei Yu, Jie Luo, Guang-Qian Xiao, Chawnshang Chang, Jun Qi, Shuyuan Yeh
Summary: Vasculogenic mimicry (VM), an alternative channel for tumor nutrient supply, is associated with poor prognosis in renal cell carcinoma (RCC). Sunitinib, a tyrosine kinase inhibitor (TKI), has been reported to induce VM formation by up-regulating estrogen receptor beta (ERβ) expression. This study showed that treatment with sunitinib and another TKI, axitinib, also induced ERβ expression in RCC cell lines. Clinical RCC patients with higher ERβ expression were more likely to have VM. Mechanistically, TKI-induced ERβ up-regulated the circular RNA DGKD, which enhanced VM formation by increasing VE-cadherin expression. Targeting circDGKD intercepted sunitinib-induced RCC VM formation and improved survival in an animal model.
Article
Cell Biology
Lei Chen, Yin Sun, Min Tang, Denglong Wu, Zhendong Xiang, Chi-Ping Huang, Bosen You, Dongdong Xie, Qinglin Ye, Dexin Yu, Chawnshang Chang
Summary: This study found that high-dose androgens can suppress the growth of Enzalutamide-resistant (EnzR) castration-resistant prostate cancer (CRPC) cells. The mechanism involves the transcriptional regulation of the circRNA-BCL2 host gene BCL2, which in turn affects the expression of miRNA-198 and modulates the expression of AMBRA1. This leads to the induction of autophagic cell death and the suppression of EnzR CRPC cell growth.
CELL DEATH DISCOVERY
(2022)
Article
Cell Biology
Yang Yang, Jindong Sheng, Shuai Hu, Yun Cui, Jing Xiao, Wei Yu, Jing Peng, Wenke Han, Qun He, Yu Fan, Yuanjie Niu, Jun Lin, Ye Tian, Chawnshang Chang, Shuyuan Yeh, Jie Jin
Summary: This study identified the histopathological characteristics and molecular mechanisms underlying accelerated progression of benign prostatic hyperplasia (BPH). Increased stromal components and prostatic fibrosis, accompanied by higher myofibroblast accumulation and collagen deposition, were found to be the main features of accelerated progressive BPH tissues. Mechanism dissection revealed that higher expression of CYP19 and G protein-coupled estrogen receptor (GPER) with higher estrogen biosynthesis contribute to the progression of BPH. Targeting the CYP19/estrogen/GPER/G alpha i signaling axis may provide new personalized therapeutics for better suppressing the progression of BPH.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Fu-Ju Chou, ChangYi Lin, Hao Tian, WanYing Lin, Bosen You, Jieyang Lu, Deepak Sahasrabudhe, Chi-Ping Huang, Vanessa Yang, Shuyuan Yeh, Yuanjie Niu, Chawnshang Chang
CELL DEATH & DISEASE
(2020)
Article
Cell Biology
Changyi Lin, Fu-Ju Chou, Jieyang Lu, Wanying Lin, Matthew Truong, Hao Tian, Yin Sun, Jie Luo, Rachel Yang, Yuanjie Niu, Rosa Nadal, Emmanuel S. Antonarakis, Carlos Cordon-Cardo, Deepak Sahasrabudhe, Chi-Ping Huang, Shuyuan Yeh, Gonghui Li, Chawnshang Chang