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)
Review
Oncology
Carole Luthold, Tarek Hallal, David P. Labbe, Francois Bordeleau
Summary: Prostate cancer affects a large number of men worldwide. Understanding the mechanisms of disease progression and therapy resistance is crucial for developing effective treatments. Alterations in the extracellular matrix, particularly stiffening, play a role in prostate cancer progression. This review examines the association between extracellular matrix stiffening and disease progression and castration resistance in prostate cancer.
Article
Biochemistry & Molecular Biology
Sarina Cameron, Genevieve Deblois, James R. Hawley, Aditi Qamra, Stanley Zhou, Seyed Ali Madani Tonekaboni, Alexander Murison, Romy Van Vliet, Juan Liu, Jason W. Locasale, Mathieu Lupien
Summary: Predicting and treating recurrence in intermediate-risk prostate cancer patients is challenging. This study found that chronic hypoxia leads to an androgen-independent state in prostate cancer cells, promoting cancer progression. These findings may provide additional strategies for treating hypoxic prostate cancer.
Article
Biochemistry & Molecular Biology
Tianhong Pan, Song-Chang Lin, Yu-Chen Lee, Guoyu Yu, Jian H. Song, Jing Pan, Mark Titus, Robert L. Satcher, Theocharis Panaretakis, Christopher Logothetis, Li-Yuan Yu-Lee, Sue-Hwa Lin
Summary: The study demonstrates that statins can reduce bone marrow adiposity and slow down the progression of prostate cancer in bones. By affecting the transition of BMSC to adipocytes, the progression of PCa may be delayed.
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
Oncology
Javier Pozas, Sara Alvarez Rodriguez, Victor Albarran Fernandez, Javier Burgos, Matteo Santoni, Ray Manneh Kopp, Javier Molina-Cerrillo, Teresa Alonso-Gordoa
Summary: This review provides an overview of the current state of androgen inhibition in the treatment of advanced prostate cancer and discusses the mechanisms of resistance to approved antiandrogen drugs. It also summarizes the main research approaches in the field of androgen receptor inhibition to overcome resistance and explores potential new drugs under investigation.
Review
Biochemistry & Molecular Biology
Francesco Lasorsa, Nicola Antonio di Meo, Monica Rutigliano, Matteo Ferro, Daniela Terracciano, Octavian Sabin Tataru, Michele Battaglia, Pasquale Ditonno, Giuseppe Lucarelli
Summary: Prostate cancer is a common malignancy in men and a leading cause of cancer death. The cancer cells have specific metabolic characteristics, including increased lipogenesis, cholesterogenesis, and reliance on glutamine. The tumor microenvironment also plays a role in cancer progression through interactions between cancer and stromal cells. The use of multi-omic approaches can provide a comprehensive understanding of the metabolic changes in prostate cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Hiroaki Iwamoto, Kouji Izumi, Takashi Shimada, Hiroshi Kano, Suguru Kadomoto, Tomoyuki Makino, Renato Naito, Hiroshi Yaegashi, Kazuyoshi Shigehara, Yoshifumi Kadono, Atsushi Mizokami
Summary: In castration-resistant prostate cancer patients, the incidence of new visceral metastasis increases significantly with the number of treatments received, resulting in shorter survival time for patients with new metastasis post-treatment. Risk factors for visceral metastasis include T stage, M stage, age, and treatment history.
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
Medicine, Research & Experimental
Sue Jin Moon, Byong Chang Jeong, Hwa Jin Kim, Joung Eun Lim, Hye-Jeong Kim, Ghee Young Kwon, Joshua A. Jackman, Jeong Hoon Kim
Summary: The study identified BCT as a potent inhibitor targeting both AR-FL and AR-V7 activities in CRPC, effectively suppressing tumor growth and metastasis. Mechanistically, BCT disrupts the interaction of HSP90 with AR-FL/AR-V7, leading to their degradation and showing promising therapeutic potential against CRPC.
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
Pharmacology & Pharmacy
Maoping Cai, Xian-Lu Song, Xin-An Li, Mingkun Chen, Jiading Guo, Dong Hua Yang, Zhanghui Chen, Shan-Chao Zhao
Summary: Castration-resistant prostate cancer (CRPC), especially metastatic CRPC (mCRPC), is a common and deadly malignancy in men worldwide. The natural or acquired drug resistance of CRPC makes clinical treatment challenging. Understanding the mechanisms of drug resistance in mCRPC is essential for developing effective therapeutic strategies. This review focuses on new insights in mCRPC treatment and discusses the mechanisms governing resistance to new drugs, such as taxanes, androgen receptor signaling inhibitors (ARSIs), and poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). Strategies to overcome drug resistance based on these mechanisms are also discussed.
DRUG RESISTANCE UPDATES
(2023)
Article
Oncology
Zemin Hou, Shengsong Huang, Zhenfei Li
Summary: Androgens are crucial in the development of prostate cancer, and targeting steroidogenesis and the androgen receptor has been effective in delaying disease progression. New generation androgen receptor pathway inhibitors like abiraterone and enzalutamide continue to emphasize the role of the androgen-AR axis, even in cases of resistance. The importance of this axis in managing the disease after resistance to current treatments, particularly in neuroendocrine prostate cancer, remains uncertain.
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
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
Biochemistry & Molecular Biology
Manqi Zhang, Egla Suarez, Judy L. Vasquez, Lubov Nathanson, Leif E. Peterson, Kimal Rajapakshe, Paul Basil, Nancy L. Weigel, Cristian Coarfa, Irina U. Agoulnik
Article
Biochemistry & Molecular Biology
Judy L. Vasquez, Yanhao Lai, Thirunavukkarasu Annamalai, Zhongliang Jiang, Manqi Zhang, Ruipeng Lei, Zunzhen Zhang, Yuan Liu, Yuk-Ching Tse-Dinh, Irina U. Agoulnik
Article
Multidisciplinary Sciences
Manqi Zhang, Yanhao Lai, Judy L. Vasquez, Dominic I. James, Kate M. Smith, Ian D. Waddell, Donald J. Ogilvie, Yuan Liu, Irina U. Agoulnik
SCIENTIFIC REPORTS
(2020)
Article
Cell Biology
Zhongliang Jiang, Yanhao Lai, Jill M. Beaver, Pawlos S. Tsegay, Ming-Lang Zhao, Julie K. Horton, Marco Zamora, Hayley L. Rein, Frank Miralles, Mohammad Shaver, Joshua D. Hutcheson, Irina Agoulnik, Samuel H. Wilson, Yuan Liu
Article
Multidisciplinary Sciences
Yasemin Ceyhan, Manqi Zhang, Jingtao Guo, Carlos G. Sandoval, Jean Vacher, Elena M. Kaftanovskaya, Alexander I. Agoulnik, Irina U. Agoulnik
Article
Biology
Manqi Zhang, Yasemin Ceyhan, Elena M. Kaftanovskaya, Judy L. Vasquez, Jean Vacher, Filip K. Knop, Lubov Nathanson, Alexander I. Agoulnik, Michael M. Ittmann, Irina U. Agoulnik
Summary: Research has shown that INPP4B signaling can protect mice from diet-induced metabolic dysfunction and help prevent multiple cancers associated with this condition.
COMMUNICATIONS BIOLOGY
(2021)
Meeting Abstract
Biochemistry & Molecular Biology
Maria Esteban-Lopez, Kenneth Wilson, Courtney Myhr, Elena Kaftanovskaya, Mark Henderson, Noel Southall, Xin Hu, Elena Barnaeva, Mare Ferrer, David Kim
Review
Reproductive Biology
Yasemin Ceyhan, Manqi Zhang, Carlos G. Sandoval, Alexander Agoulnik, Irina U. Agoulnik
Summary: Phosphatidylinositol polyphosphate phosphatases (PI phophatases) are important for testicular function and spermatogenesis. They regulate various processes such as cellular signaling and cytoskeletal organization. Deficiency of PI phosphatases can lead to infertility in both mice and humans.
BIOLOGY OF REPRODUCTION
(2022)
Editorial Material
Oncology
Margarita M. Ivanova, Irina U. Agoulnik, Matilde E. LLeonart
FRONTIERS IN ONCOLOGY
(2022)
Article
Biology
Maria Esteban-Lopez, Kenneth J. Wilson, Courtney Myhr, Elena M. Kaftanovskaya, Mark J. Henderson, Noel T. Southall, Xin Xu, Amy Wang, Xin Hu, Elena Barnaeva, Wenjuan Ye, Emmett R. George, John T. Sherrill, Marc Ferrer, Roy Morello, Irina U. Agoulnik, Juan J. Marugan, Alexander Agoulnik
Summary: Specific small molecule RXFP2 agonists induce proper development of reproduction and bone through experimental validation, providing potential for oral administration.
COMMUNICATIONS BIOLOGY
(2022)
Article
Oncology
Manqi Zhang, Yasemin Ceyhan, Shenglin Mei, Taghreed Hirz, David B. Sykes, Irina U. Agoulnik
Summary: Prostate cancer is driven by multiple genetic alterations, and the loss of INPP4B and PTEN is a common tumor suppressor loss in prostate cancer. The loss of INPP4B and PTEN triggers different compensatory responses in prostate tissue.
Meeting Abstract
Oncology
Yasemin Ceyhan, Manqi Zhang, Irina U. Agoulnik
Meeting Abstract
Oncology
Yasemin Ceyhan, Manqi Zhang, Irina U. Agoulnik
Meeting Abstract
Environmental Sciences
C. Marin, Y. Ceyhan, I Agoulnik, Y. Liu
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2021)
Meeting Abstract
Environmental Sciences
A. Shariff, N. Diaz, Y. Lai, I Agoulnik, Y. Liu
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2021)