Review
Oncology
Masaki Shiota, Satoshi Endo, Leandro Blas, Naohiro Fujimoto, Masatoshi Eto
Summary: Castration resistance is caused by the abnormal activation of androgen receptor (AR) signaling through intracrine activation of androgen precursors from adrenal glands. To address this, novel AR pathway inhibitors (ARPIs) have been developed to suppress androgen synthesis or AR activation. However, resistance to these ARPIs can occur due to the persistent androgen environment despite intensive AR signaling suppression.
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
(2023)
Article
Biochemistry & Molecular Biology
Michele Iuliani, Sonia Simonetti, Giulia Ribelli, Silvia Cavaliere, Bruno Vincenzi, Giuseppe Tonini, Francesco Pantano, Daniele Santini
Summary: Abiraterone, a selective inhibitor of androgen biosynthesis, has been approved for the treatment of prostate cancer. This study provides evidence that abiraterone can inhibit prostate cancer cell proliferation through modulation of multiple osteoblast proliferative signals.
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
Biochemistry & Molecular Biology
Chaima Cherif, Dang Tan Nguyen, Clement Paris, Thi Khanh Le, Thibaud Sefiane, Nadine Carbuccia, Pascal Finetti, Max Chaffanet, Abdessamad El Kaoutari, Julien Vernerey, Ladan Fazli, Martin Gleave, Mohamed Manai, Philippe Barthelemy, Daniel Birnbaum, Francois Bertucci, David Taieb, Palma Rocchi
Summary: Menin (MEN1) protein is highly regulated by HSP27, overexpressed in high-grade PC and CRPC, and high MEN1 mRNA expression is associated with decreased biochemical relapse-free and overall survival. Silencing Menin helps inhibit CRPC cell proliferation, tumor growth, and restore chemotherapeutic sensitivity.
Article
Oncology
Matti Annala, Sinja Taavitsainen, Daniel J. Khalaf, Gillian Vandekerkhove, Kevin Beja, Joonatan Sipola, Evan W. Warner, Cameron Herberts, Amanda Wong, Simon Fu, Daygen L. Finch, Conrad D. Oja, Joanna Vergidis, Muhammad Zulfiqar, Bernhard J. Eigl, Christian K. Kollmansberger, Matti Nykter, Martin E. Gleave, Kim N. Chi, Alexander W. Wyatt
Summary: In patients with mCRPC, sequential AR signaling inhibitor treatment leads to continuous evolution of the AR genotype, driving acquired resistance mainly through changes in the AR gene.
CLINICAL CANCER RESEARCH
(2021)
Review
Endocrinology & Metabolism
Xiangyun You, Shan Huang, Xin'an Wang, Cheng Yi, Niandong Gong, Junfeng Yu, Chengdang Xu, Zhendong Xiang
Summary: Bipolar androgen therapy (BAT) is an effective and safe treatment for castration-resistant prostate cancer patients who have progressed after abiraterone or enzalutamide. BAT can restore patients' sensitivity to subsequent endocrine therapy and improve overall survival and quality of life. Meta-analysis results showed that patients who underwent BAT achieved a PSA50 response rate of 27%, an ORR of 34%, and a grade >= 3 adverse event incidence of 14%.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Oncology
Anthony Serritella, Daniel Shevrin, Elisabeth Heath, James L. Wade, Elia Martinez, Amanda Anderson, Joseph Schonhoft, Yen-Lin Chu, Theodore Karrison, Walter M. Stadler, Russell Z. Szmulewitz
Summary: This study evaluated the effectiveness of dual androgen receptor (AR) and glucocorticoid receptor (GR) antagonism in castration-resistant prostate cancer (CRPC). The combination of enzalutamide and mifepristone was found to be safe and well-tolerated, but did not meet the primary endpoint. Further research should explore the use of more specific GR antagonists combined with AR antagonists in earlier disease stages.
CLINICAL CANCER RESEARCH
(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
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.
Article
Oncology
Jun Li, Nan Liu, Hong Zhou, Peng Xian, Yanping Song, Xianli Tang, Yuan Li, Michael Basler
Summary: This study found that immunoproteasome inhibition has a significant effect on suppressing the progression of castration-resistant prostate cancer (CRPC). The results showed that immunoproteasome inhibition prevents CRPC progression by suppressing inflammation and inducing apoptosis of CRPC cells through activating the unfolded protein response.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Sarah E. Kohrt, Wisam N. Awadallah, Robert A. Phillips, Thomas C. Case, Renjie Jin, Jagpreet S. Nanda, Xiuping Yu, Peter E. Clark, Yajun Yi, Robert J. Matusik, Philip D. Anderson, Magdalena M. Grabowska
Summary: A short hairpin RNA screen identified 11 genes supporting enzalutamide resistance, with validation experiments confirming the roles of ACAT1, MAP3K11, and PSMD12 in vitro. Inhibition of MAP3K11 in combination with enzalutamide led to increased cell death, suggesting potential therapeutic strategies for castration-resistant prostate cancer.
MOLECULAR CANCER THERAPEUTICS
(2021)
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
Urology & Nephrology
E. M. Kwan, I. A. Thangasamy, J. Teh, O. Alghazo, N. J. Sathianathen, N. Lawrentschuk, A. A. Azad
Summary: The management of metastatic castration-naive prostate cancer has drastically improved in the last decade due to the introduction of potent systemic therapies, with both chemohormonal approaches and AR pathway inhibitors showing promising results. Decision-making for treatment should take into consideration various factors and ongoing research into novel therapeutic options is expected to further enhance patient outcomes and quality of life.
WORLD JOURNAL OF UROLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Thi Khanh Le, Chaima Cherif, Kenneth Omabe, Clement Paris, Francois Lannes, Stephane Audebert, Emilie Baudelet, Mourad Hamimed, Dominique Barbolosi, Pascal Finetti, Cyrille Bastide, Ladan Fazli, Martin Gleave, Francois Bertucci, David Taieb, Palma Rocchi
Summary: The heat shock protein 27 (Hsp27) plays a crucial role in the progression of castration-resistant prostate cancer (CRPC), and an antisense oligonucleotide (ASO) against Hsp27 has been evaluated in clinical trials. This study demonstrates that Hsp27 regulates the expression of the human DEAD-box protein 5 (DDX5) and identifies DDX5 as a potential therapeutic target for CRPC treatment.
Article
Oncology
Pei-Yu Li, Ying-Hao Lu, Chung-Yu Chen
Summary: This study compared the effectiveness of abiraterone and enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) using real-world data from Taiwan. The study found that enzalutamide was associated with better overall survival (OS) than abiraterone, but there was no significant difference in time to treatment failure (TTF) between the two drugs.
FRONTIERS IN ONCOLOGY
(2022)
