Article
Oncology
Maryam Labaf, Muqing Li, Lily Ting, Breelyn Karno, Songqi Zhang, Shuai Gao, Susan Patalano, Jill A. A. Macoska, Kourosh Zarringhalam, Dong Han, Changmeng Cai
Summary: This study examines the acute effects of overexpressed androgen receptor (AR) on its cistrome and transcriptome in a prostate cancer (PCa) model. The results show that overexpression of AR leads to redistribution of AR chromatin binding and activation of a distinct transcription program, including DNA damage repair pathways. The study also predicts the involvement of EZH2 in this AR reprogramming and identifies a subset of AR/EZH2 co-targeting genes that are overexpressed in castration-resistant PCa and associated with worse patient outcomes.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Nader Al-Nakouzi, Chris Kedong Wang, Htoo Zarni Oo, Irina Nelepcu, Nada Lallous, Charlotte B. Spliid, Nastaran Khazamipour, Joey Lo, Sarah Truong, Colin Collins, Desmond Hui, Shaghayegh Esfandnia, Hans Adomat, Thomas Mandel Clausen, Tobias Gustavsson, Swati Choudhary, Robert Dagil, Eva Corey, Yuzhuo Wang, Anne Chauchereau, Ladan Fazli, Jeffrey D. Esko, Ali Salanti, Peter S. Nelson, Martin E. Gleave, Mads Daugaard
Summary: Inhibition of the androgen receptor pathway leads to the upregulation of chondroitin sulfate (CS), which promotes the growth and metastasis of prostate cancer.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Tae Jin Kim, Young Hwa Lee, Kyo Chul Koo
Summary: The androgen receptor (AR) plays a crucial role in the development and progression of prostate cancer (PCa), and treatment for hormone-sensitive prostate cancer (HSPC) relies heavily on androgen deprivation therapy (ADT). Despite most patients progressing to castration-resistant prostate cancer (CRPC), studies suggest that manipulating alternative molecular pathways can help improve current treatments and develop novel therapies for CRPC management.
Article
Oncology
Jing Wei, Lijuan Yin, Jingjing Li, Jing Wang, Tianjie Pu, Peng Duan, Tzu-Ping Lin, Allen C. Gao, Boyang Jason Wu
Summary: The study reveals a reciprocal regulatory circuit between MAOA and AR in prostate cancer, with implications for cancer development and growth, particularly CRPC. Targeting MAOA may enhance the efficacy of AR-targeted therapies.
Article
Oncology
Miho Ushijima, Masaki Shiota, Takashi Matsumoto, Eiji Kashiwagi, Junichi Inokuchi, Masatoshi Eto
Summary: PMD-026, a novel ribosomal S6 kinase inhibitor, shows excellent antitumor effect in castration-resistant prostate cancer by regulating the YB-1/AR signaling pathway. PMD-026 alone or in combination with the antiandrogen drug enzalutamide inhibits cell proliferation, induces apoptosis, and G2/M arrest, effectively suppressing tumor growth.
Article
Oncology
Almudena Zapatero, Ana Alvarez, Araceli Guerrero, Xavier Maldonado, Carmen Gonzalez San Segundo, Maria A. Cabeza, Carmen Martin de Vidales, Josep M. Sole, Agusti Pedro Olive, Francesc Casas, Ana Boladeras, Maria L. Vazquez de la Torre, Susana Vara, Felipe A. Calvo
Summary: The study found that additional serum testosterone suppression below 20 ng/dL did not necessarily lead to better outcomes compared to levels between 20-49 ng/dL in patients with localized prostate cancer. Time to testosterone recovery after androgen deprivation therapy and high-dose radiotherapy did not impact clinical failure.
RADIOTHERAPY AND ONCOLOGY
(2021)
Article
Oncology
Neele Wuestmann, Konstantin Seitzer, Verena Humberg, Julia Vieler, Norbert Grundmann, Julie Steinestel, Dorothee Tiedje, Stefan Duensing, Laura-Maria Krabbe, Martin Boegemann, Andres Jan Schrader, Christof Bernemann, Katrin Schlack
Summary: This study found that the level of AR-FL and the appearance and increase of AR-Vs are associated with elevated levels of AR pre-mRNA in prostate cancer cells. The levels of AR-FL and AR-Vs also increase during disease progression. In patients undergoing ARTA treatment, AR-FL shows prognostic value but not predictive value. Additionally, even AR-V positive patients show a significant clinical response to ARTA treatment. Therefore, AR-FL and AR-V may be considered as prognostic biomarkers in mCRPC patients, but not predictive biomarkers.
BIOMARKER RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Helen Saxby, Stergios Boussios, Christos Mikropoulos
Summary: Stereotactic ablative body radiotherapy (SABR) plays an important role in the treatment of oligometastatic prostate cancer, and combining it with androgen deprivation therapy (ADT) can improve treatment outcomes. By examining data, we can find a strategy to overcome radiotherapy resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Xu Li, Shu Zhuo, Yong Suk Cho, Yuchen Liu, Yingzi Yang, Jian Zhu, Jin Jiang
Summary: Hippo signaling inhibits the oncogenic potential of YAP/TAZ-TEAD transcriptional complex, restricting tumor growth. In AR-positive prostate cancer, YAP acts as a tumor suppressor by counteracting TEAD-mediated AR signaling. YAP competes with AR for TEAD binding, disrupting AR-TEAD interaction and preventing TEAD from promoting AR signaling. Targeting the Hippo signaling pathway may provide a therapeutic opportunity to treat therapy resistant AR variants-driven prostate cancer.
Review
Oncology
Matt Shirley
Summary: Relugolix (Orgovyx(R)) is an orally active nonpeptide GnRH receptor antagonist that provides rapid testosterone suppression and is indicated in the USA and EU for the treatment of advanced prostate cancer. In a phase III trial, relugolix demonstrated sustained castration rates >90% over 48 weeks, which were comparable to leuprolide, but with potentially improved cardiac safety. With its rapid and sustained testosterone suppression, oral administration, and potential cardiovascular benefits, relugolix presents a valuable treatment option for men with advanced prostate cancer.
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)
Review
Oncology
Daniel J. George, David P. Dearnaley
Summary: Relugolix, a GnRH receptor antagonist, reduces testosterone levels without an initial increase, and has been shown in clinical studies to lower testosterone levels more quickly than leuprolide acetate. Men treated with relugolix also have a lower risk of heart attacks, strokes, and death compared to those treated with leuprolide acetate. This new treatment option offers a faster recovery of testosterone levels post-treatment.
Review
Chemistry, Medicinal
Tomoyuki Tatenuma, Hiroshi Miyamoto
Summary: Androgen deprivation therapy is the main treatment for advanced prostate cancer, and relugolix has been developed as an oral alternative. Previous studies have shown comparable efficacy between relugolix and other gonadotropin-releasing hormone antagonists or agonists. This review summarizes the design, development, and therapeutic application of relugolix and discusses its potential as a promising oral alternative to injectable therapy.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2023)
Review
Oncology
Fred Saad, Neal D. Shore
Summary: Relugolix, the newest GnRH antagonist, offers rapid and sustained castration without the testosterone surge seen with LHRH agonists, potentially reducing the need for additional anti-androgen therapy. Data from phase III studies also suggest improved cardiovascular safety profile compared to traditional LHRH agonists, indicating a potential new standard of care for prostate cancer management.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Thanh Nguyen, Dhivya Sridaran, Surbhi Chouhan, Cody Weimholt, Audrey Wilson, Jingqin Luo, Tiandao Li, John Koomen, Bin Fang, Nagireddy Putluri, Arun Sreekumar, Felix Y. Feng, Kiran Mahajan, Nupam P. Mahajan
Summary: This study reveals a new mechanism of inhibiting androgen synthesis by phosphorylated SREBF1 protein, which affects the development and treatment of prostate cancer.
NATURE COMMUNICATIONS
(2023)