Article
Oncology
Christos Kakouratos, Dimitra Kalamida, Ioannis Lamprou, Erasmia Xanthopoulou, Christos Nanos, Alexandra Giatromanolaki, Michael Koukourakis
Summary: In vitro and in vivo experiments showed that apalutamide has superior radio-sensitising activity compared to bicalutamide in combination with radiotherapy for prostate cancer. Clinical studies are encouraged to determine whether replacing bicalutamide with apalutamide can improve curability rates.
BRITISH JOURNAL OF CANCER
(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)
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.
Article
Oncology
Zhengfang Liu, Cheng Liu, Keqiang Yan, Jikai Liu, Zhiqing Fang, Yidong Fan
Summary: The huaier extract demonstrated potent antiproliferative effects in both hormone sensitive prostate cancer (HSPC) and castration-resistant prostate cancer (CRPC) cells by downregulating AR-FL and AR-V7 mRNA levels via targeting the SMYD3 signaling pathway, and enhancing proteasome-mediated protein degradation of AR-FL and AR-V7 by downregulating USP14. Additionally, the extract inhibited AR transcriptional activity and their nuclear translocation, and could re-sensitize enzalutamide-resistant prostate cancer cells to enzalutamide treatment in vitro and in vivo models.
FRONTIERS IN ONCOLOGY
(2021)
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)
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
Biochemistry & Molecular Biology
Atsumi Ota, Mina Kawai, Yudai Kudo, Jin Segawa, Manami Hoshi, Shinya Kawano, Yuta Yoshino, Kenji Ichihara, Masaki Shiota, Naohiro Fujimoto, Toshiyuki Matsunaga, Satoshi Endo, Akira Ikari
Summary: In this study, the researchers identified a compound called artepillin C (ArtC) found in Brazilian green propolis that has anti-androgen activity and can inhibit the growth of prostate cancer cells. ArtC also enhances the sensitivity of resistant cells to apalutamide, a novel AR antagonist, by inducing cell death. These findings suggest that ArtC from Brazilian green propolis has the potential to improve prostate cancer therapy.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Oncology
Marco A. De Velasco, Yurie Kura, Naomi Ando, Noriko Sako, Eri Banno, Kazutoshi Fujita, Masahiro Nozawa, Kazuhiro Yoshimura, Kazuko Sakai, Kazuhiro Yoshikawa, Kazuto Nishio, Hirotsugu Uemura
Summary: The study demonstrates potent antitumor activity of apalutamide in early-stage and late-stage castration-naive prostate cancer models, but limited efficacy in castration-resistant prostate cancer. Additionally, the therapeutic potential of combined AR/AKT inhibition was shown to be more promising in vitro than in vivo, possibly due to upregulation of STAT3 and PIM-1.
Article
Urology & Nephrology
Alexander Pan, Rachel E. Reingold, Jimmy L. Zhao, Andrea Moy, Lukas Kraehenbuehl, George Dranitsaris, Sean M. McBride, Howard Scher, Marisa A. Kollmeier, Han Xiao, Dana E. Rathkopf, Mario E. Lacouture
Summary: Patients with prostate cancer treated with apalutamide frequently develop dermatological adverse events, such as rash. Common adverse events include maculopapular rashes and xerosis. Clinical trial patients and those receiving abiraterone/prednisone are more likely to experience these events. Most adverse events can be managed with topical or oral steroids.
JOURNAL OF UROLOGY
(2022)
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
Oncology
Wout Devlies, Florian Handle, Gaetan Devos, Steven Joniau, Frank Claessens
Summary: This review investigates the existing methods to study treatment resistance to androgen receptor targeted therapies in prostate cancer, including the role of preclinical models and understanding of resistance mechanisms. Understanding resistance will greatly improve insights into tumor pathophysiology and future treatment strategies in prostate cancer.
Article
Pharmacology & Pharmacy
Yongbao Wei, Ruochen Zhang, Dewen Zhong, Zhensheng Chen, Gen Chen, Minggen Yang, Le Lin, Tao Li, Liefu Ye, Lili Chen, Qingguo Zhu
Summary: The efficacy and safety of neoadjuvant therapy in improving the resectability rate of radical prostatectomy (RP) in cases of unresectable primary tumors of prostate cancer (PCa) were evaluated in this retrospective study. The results supported the use of apalutamide as a neoadjuvant therapy, which improved the success rate of RP without significant increase in perioperative complications. However, further clinical research is needed to confirm the clinical value and benefit for survival.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Cell Biology
Yuan Liu, Cuifu Yu, Zhenlong Shao, Xiaohong Xia, Tumei Hu, Weiyao Kong, Xiaoyue He, Wenshuang Sun, Yuanfei Deng, Yuning Liao, Hongbiao Huang
Summary: AR-V7, a crucial factor in driving CRPC, can be effectively degraded by nobiletin through inducing G0/G1 phase arrest and enhancing sensitivity of cells to enzalutamide, offering a novel approach for treating CRPC.
CELL DEATH & DISEASE
(2021)
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
Oncology
Martin K. Bakht, Yasutaka Yamada, Sheng-Yu Ku, Varadha Balaji Venkadakrishnan, Joshua A. Korsen, Teja M. Kalidindi, Kei Mizuno, Shin Hye Ahn, Ji-Heui Seo, Maria Mica Garcia, Francesca Khani, Olivier Elemento, Henry W. W. Long, Alain Chaglassian, Nagavarakishore Pillarsetty, Jason S. Lewis, Matthew Freedman, Anthony P. Belanger, Quang-De Nguyen, Himisha Beltran
Summary: Beltran and colleagues explore the regulatory roles of HOXB13 and AR in the heterogeneous expression of PSMA in castration-resistant prostate cancer. They found that PSMA expression is lost in a subset of CRPC patients and is influenced by the microenvironment. The study also identifies HOXB13 as an upstream regulator of PSMA, independent of AR expression. These findings provide insights for the development of PSMA-targeted therapies and complementary biomarkers.
Article
Endocrinology & Metabolism
Pedro Isaacsson Velho, John L. Silberstein, Mark C. Markowski, Jun Luo, Tamara L. Lotan, William B. Isaacs, Emmanuel S. Antonarakis
Review
Pharmacology & Pharmacy
Pedro Isaacsson Velho, Emmanuel S. Antonarakis
EXPERT REVIEW OF CLINICAL PHARMACOLOGY
(2018)
Article
Urology & Nephrology
Pedro Isaacsson Velho, Fahad Qazi, Sayeedul Hassan, Michael A. Carducci, Samuel R. Denmeade, Mark C. Markowski, Daniel L. Thorek, Theodore L. DeWeese, Daniel Y. Song, Phuoc T. Tran, Mario A. Eisenberger, Emmanuel S. Antonarakis
Article
Urology & Nephrology
Emmanuel S. Antonarakis, Farah Shaukat, Pedro Isaacsson Velho, Harsimar Kaur, Eugene Shenderov, Drew M. Pardoll, Tamara L. Lotan
Article
Urology & Nephrology
Pedro Isaacsson Velho, Wei Fu, Hao Wang, Nooshin Mirkheshti, Fahad Qazi, Fabiola A. S. Lima, Farah Shaukat, Michael A. Carducci, Samuel R. Denmeade, Channing J. Paller, Mark C. Markowski, Catherine H. Marshall, Mario A. Eisenberger, Emmanuel S. Antonarakis
Article
Endocrinology & Metabolism
Channing J. Paller, Danilo Piana, James R. Eshleman, Stacy Riel, Samuel R. Denmeade, Pedro Isaacsson Velho, Steven P. Rowe, Martin G. Pomper, Emmanuel S. Antonarakis, Jun Luo, Mario A. Eisenberger
Article
Endocrinology & Metabolism
Eugene Shenderov, Pedro Isaacsson Velho, Anas H. Awan, Hao Wang, Nooshin Mirkheshti, Tamara L. Lotan, Michael A. Carducci, Drew M. Pardoll, Mario A. Eisenberger, Emmanuel S. Antonarakis
Article
Endocrinology & Metabolism
Emily Nizialek, Su Jin Lim, Hao Wang, Pedro Isaacsson Velho, Srinivasan Yegnasubramanian, Emmanuel S. Antonarakis
Summary: The study found that TP53 DN mutations were the strongest predictor of negative outcomes in men with mHSPC, while SPOP mutations were associated with improved outcomes. Specific gene mutations were prognostic of outcomes in secondary, but not primary, mHSPC.
Article
Oncology
Aline B. L. Gongora, Catherine H. Marshall, Pedro Isaacsson Velho, Carlos D. H. Lopes, Jose F. Marin, Anamaria A. Camargo, Diogo A. Bastos, Emmanuel S. Antonarakis
Summary: Pathogenic alterations in CDK12 have been associated with improved response to immunotherapy in patients with metastatic castration-resistant prostate cancer, but the responses are modest.
CLINICAL GENITOURINARY CANCER
(2022)
Article
Endocrinology & Metabolism
Mari Nakazawa, Mike Fang, Catherine H. Marshall, Tamara L. Lotan, Pedro Isaacsson Velho, Emmanuel S. Antonarakis
Summary: Prostate cancers with SPOP mutations represent a unique subset with absent ERG fusions and frequent Wnt pathway alterations, showing potentially greater dependency on androgen signaling and enhanced responsiveness to androgen deprivation therapy. Patients with SPOP alterations have the best outcomes when there are no other concurrent mutations.
Review
Biochemistry & Molecular Biology
Nima Nabavi, Seied Rabi Mahdavi, Mohammad Afshar Ardalan, Mohsen Chamanara, Reza Mosaed, Aline Lara, Diogo Bastos, Sara Harsini, Emran Askari, Pedro Isaacsson Velho, Hamed Bagheri
Summary: Androgen deprivation therapy (ADT) is the main treatment for advanced prostate cancer, but the development of castration-resistant prostate cancer is inevitable. Using novel hormonal agents may have long-term toxicities and trigger the selection of androgen receptor-independent cells. Bipolar androgen therapy (BAT) is a promising approach that involves alternating testosterone levels to inhibit prostate cancer growth and re-sensitize patients to previous therapies.
Article
Oncology
Matthew P. Deek, Kekoa Taparra, Ryan Phillips, Pedro Isaacsson Velho, Robert W. Gao, Curtiland Deville, Daniel Y. Song, Stephen Greco, Michael Carducci, Mario Eisenberger, Theodore L. DeWeese, Samuel Denmeade, Kenneth Pienta, Channing J. Paller, Emmanuel S. Antonarakis, Kenneth R. Olivier, Sean S. Park, Phuoc T. Tran, Bradley J. Stish
Summary: SABR treatment for oligoprogressive castrate-resistant prostate cancer patients can improve outcomes and enhance cancer control. Compared to changing systemic therapy alone, MDT showed better results in terms of time to PSA failure, time to next intervention, and distant metastasis-free survival.
EUROPEAN UROLOGY ONCOLOGY
(2021)
Article
Oncology
Pedro Isaacsson Velho, Diogo Assed Bastos, Emmanuel S. Antonarakis
Summary: The androgen signaling axis has been a key therapeutic target for advanced prostate cancer with the development of more potent AR-targeted therapies. Despite significant advances, patients often develop resistance to treatment, highlighting an ongoing need for research into novel mechanisms to overcome resistance.
CLINICAL ADVANCES IN HEMATOLOGY & ONCOLOGY
(2021)