Article
Cell Biology
Sadia Sarwar, Viacheslav M. Morozov, Hamsa Purayil, Yehia Daaka, Alexander M. Ishov
Summary: Androgen ablation therapy is the standard treatment for newly diagnosed prostate cancer patients. However, the relapse of castration-resistant prostate cancer (CRPC) often leads to metastasis and disease lethality. Current therapies for metastatic CRPC are limited due to resistance to Taxanes. In this study, we found that inhibition of the mitotic checkpoint kinase Mps1 enhances the efficacy of Taxanes treatment, providing a potential new therapeutic target for managing therapy-resistant metastatic CRPC.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Yu-Yun Shao, Nai-Yun Sun, Yung-Ming Jeng, Yao-Ming Wu, Chiun Hsu, Chih-Hung Hsu, Hey-Chi Hsu, Ann-Lii Cheng, Zhong-Zhe Lin
Summary: High Eg5 expression is associated with poor prognosis in HCC, while low Eg5 expression is linked to better overall and disease-free survival. LGI-147 reduces cell growth through cell cycle arrest and apoptosis and induces the accumulation of abnormal mitotic cells.
Article
Multidisciplinary Sciences
Fanying Tang, Duo Xu, Shangqian Wang, Chen Khuan Wong, Alexander Martinez-Fundichely, Cindy J. Lee, Sandra Cohen, Jane Park, Corinne E. Hill, Kenneth Eng, Rohan Bareja, Teng Han, Eric Minwei Liu, Ann Palladino, Wei Di, Dong Gao, Wassim Abida, Shaham Beg, Loredana Puca, Maximiliano Meneses, Elisa de Stanchina, Michael F. Berger, Anuradha Gopalan, Lukas E. Dow, Juan Miguel Mosquera, Himisha Beltran, Cora N. Sternberg, Ping Chi, Howard Scher, Andrea Sboner, Yu Chen, Ekta Khurana
Summary: This study classified CRPC into different subtypes using ATAC-seq, RNA-seq, and DNA sequencing. The identified subtypes include AR-dependent, neuroendocrine, Wnt-dependent, and stem cell-like subtypes driven by AP-1 transcription factors. Transcriptomic signatures were used for patient classification, and SCL was found to be the second most common subtype of CRPC.
Article
Biochemistry & Molecular Biology
Junqing Gan, Shan Liu, Yu Zhang, Liangzi He, Lu Bai, Ran Liao, Juan Zhao, Madi Guo, Wei Jiang, Jiade Li, Qi Li, Guannan Mu, Yangjiazi Wu, Xinling Wang, Xingli Zhang, Dan Zhou, Huimin Lv, Zhengfeng Wang, Yanqiao Zhang, Cheng Qian, MeiYan Feng, Hui Chen, Qingwei Meng, Xiaoyi Huang
Summary: The high expression of miR-375 is associated with the development and drug resistance of prostate cancer. Using exosomes derived from human umbilical cord mesenchymal stem cells loaded with molecules that inhibit miR-375, the growth of prostate cancer can be repressed and resistance to drugs like enzalutamide can be reduced.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Article
Medicine, Research & Experimental
Xi Chen, Yechen Wu, Xinan Wang, Chengdang Xu, Licheng Wang, Jingang Jian, Denglong Wu, Gang Wu
Summary: This study identified CDK6 as a potential gene associated with the occurrence of EnzR CRPC using bioinformatic methods. The study also revealed that suppression of CDK6 expression may be helpful in treating EnzR CRPC.
EUROPEAN JOURNAL OF MEDICAL RESEARCH
(2022)
Review
Cell Biology
Shreyas Sridhar, Tatsuo Fukagawa
Summary: The assembly of functional kinetochore is crucial for accurate chromosome segregation during mitosis. Internal and external structures of kinetochore face multiple challenges, but linker proteins play an important role in force propagation and recruitment of outer kinetochore. Understanding these linkages and regulatory pathways is essential for understanding kinetochore structural diversity and plasticity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Ilsa M. Coleman, Navonil DeSarkar, Colm Morrissey, Li Xin, Martine P. Roudier, Erolcan Sayar, Dapei Li, Eva Corey, Michael C. Haffner, Peter S. Nelson
Summary: This study classified metastatic castration-resistant prostate cancers (mCRPC) into LumA, LumB, and Basal subtypes using the PAM50 breast cancer classification algorithm and investigated their association with treatment outcomes. The study found that the LumA subtype was enriched in TGFss and... pathways.
CLINICAL CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Hong Wang, Ji Liu, Xiaojun Zhu, Bin Yang, Zuping He, Xudong Yao
Summary: This study investigates the role of AZGP1P2, a pseudogene of AZGP1, in regulating the stemness and apoptosis of prostate cancer stem cells (PCSCs) and treatment resistance in castration-resistant prostate cancer (CRPC). The results show that upregulation of AZGP1P2 enhances the sensitivity of docetaxel treatment in CRPCs by inhibiting their stemness. Mechanistically, AZGP1P2 binds to UBA1 and RBM15 to form a compound that contributes to RBM15 protein degradation and controls the mRNA decay of TPM1 in m6A methylation. In vivo experiments further confirm the therapeutic effect of AZGP1P2 in increasing the therapeutic effect of docetaxel in CRPC. These findings suggest that AZGP1P2 mediates the stemness and apoptosis of PCSCs and promotes the therapeutic effect of docetaxel in CRPC by suppressing tumor growth and metastasis via UBA1/RBM15-mediated TPM1 mRNA decay.
Editorial Material
Biochemistry & Molecular Biology
Jonathan B. Coulter, Hariharan Easwaran
Summary: A new study in PLOS Biology suggests that combined therapy targeting EZH2 and HDACs may enhance the sensitivity of castration-resistant prostate cancer to both epigenetic and standard therapies.
Article
Cell Biology
Mithila Sawant, Kiran Mahajan, Arun Renganathan, Cody Weimholt, Jingqin Luo, Vandna Kukshal, Joseph M. Jez, Myung Sik Jeon, Bo Zhang, Tiandao Li, Bin Fang, Yunting Luo, Nicholas J. Lawrence, Harshani R. Lawrence, Felix Y. Feng, Nupam P. Mahajan
Summary: Resistance to enzalutamide in castration-resistant prostate cancer (CRPC) is a common issue without effective therapeutic options. This study reveals that acetylation at Lys(609) in the DNA binding domain of androgen receptor (AR) allows AR translocation and confers enzalutamide insensitivity. The acetylation is mediated by ACK1 kinase-mediated AR Y267 phosphorylation, which leads to positive feedback loops at both transcriptional and posttranslational levels. Inhibiting ACK1 kinase with a small-molecule inhibitor compromises enzalutamide-resistant CRPC xenograft tumor growth.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Rong Wang, Yuanyuan Mi, Jiang Ni, Yang Wang, Lingwen Ding, Xuebin Ran, Qiaoyang Sun, Soo Yong Tan, H. Phillip Koeffler, Ninghan Feng, Yong Q. Chen
Summary: The treatment of castration-resistant prostate cancer (CRPC) has always been a clinical challenge. The traditional approach is to reduce dihydrotestosterone biosynthesis or block androgen receptor (AR) signaling. However, this study suggests that the use of AR inhibitors can actually lead to drug tolerance and resistance. The up-regulation of peroxiredoxin 5 (PRDX5) is shown to promote resistance to AR inhibitors and the development of CRPC. Inhibition of PRDX5 suppresses drug-tolerant persister (DTP) cell proliferation, dampens CRPC development, and stabilizes disease progression in patients.
Article
Oncology
Frantzeska Giginis, Joshua Wang, Aaron Chavez, Manuela Martins-Green
Summary: Prostate Cancer (PCa) is the second most prevalent cancer in the world. Currently, most treatments for PCa involve Androgen Deprivation Therapy (ADT) which is not effective for metastatic Castration-Resistant Prostate Cancer (mCRPC). Decreasing the enzyme catalase, which reduces oxidative stress levels, has the potential to provide another target for Prostate Cancer therapy.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Article
Oncology
Duy T. Nguyen, Wei Yang, Arun Renganathan, Cody Weimholt, Duminduni H. Angappulige, Thanh Nguyen, Robert W. Sprung, Gerald L. Andriole, Eric H. Kim, Nupam P. Mahajan, Kiran Mahajan
Summary: This study reveals that HOXB13 exacerbates the antagonism of androgen receptor (AR) in castration-resistant prostate cancers (CRPC), and identifies a novel lysine 13 (K13) acetylation in HOXB13. Acetylated K13-HOXB13 serves as a clinical biomarker for the development of CRPC and promotes the expression of lineage, diagnostic, CRPC-promoting, and angiogenesis genes. The HOXB13 target ACK1 could be a potential therapeutic target for inhibiting CRPC growth.
CLINICAL CANCER RESEARCH
(2022)
Review
Endocrinology & Metabolism
Anna E. Harris, Veronika M. Metzler, Jennifer Lothion-Roy, Dhruvika Varun, Corinne L. Woodcock, Daisy B. Haigh, Chantelle Endeley, Maria Haque, Michael S. Toss, Mansour Alsaleem, Jenny L. Persson, Lorraine J. Gudas, Emad Rakha, Brian D. Robinson, Francesca Khani, Laura M. Martin, Jenna E. Moyer, Juliette Brownlie, Srinivasan Madhusudan, Cinzia Allegrucci, Victoria H. James, Catrin S. Rutland, Rupert G. Fray, Atara Ntekim, Simone de Brot, Nigel P. Mongan, Jennie N. Jeyapalan
Summary: This article summarizes the current status of anti-androgen clinical trials, discusses the potential of novel combination therapies, and explores recent advances in the development of novel epigenetic targeted therapies that may prevent or reverse disease progression in patients with advanced prostate cancer.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Nur Erysha Sabrina Jefferi, Asma' 'Afifah Shamhari, Nur Khayrin Zulaikha Noor Azhar, Joyce Goh Yi Shin, Nur Annisa Mohd Kharir, Muhammad Afiq Azhar, Zariyantey Abd Hamid, Siti Balkis Budin, Izatus Shima Taib
Summary: Castration-resistant prostate cancer (CRPC) is an aggressive stage of prostate cancer, where PCa cells invade nearby or other parts of the body after androgen deprivation therapy (ADT). Recent studies suggest the involvement of the estrogen pathway in CRPC development, specifically through estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta) regulation. This review article summarizes the underlying processes involving ER alpha and ER beta in CRPC development, including castration-resistant mechanisms and available medication modification to mitigate CRPC progression, aiming to guide future research and treatment.