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, General & Internal
Mallika Marar, Qi Long, Ronac Mamtani, Vivek Narayan, Neha Vapiwala, Ravi B. Parikh
Summary: This study investigated the differences in outcomes between African American and non-Hispanic White men with metastatic castration-resistant prostate cancer (mCRPC) who received first-line abiraterone therapy. The results showed that African American men had a higher overall survival when receiving first-line abiraterone compared to non-Hispanic White men. However, there was a difference in outcomes between the two groups for first-line enzalutamide treatment.
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
Andrology
Koji Hatano, Norio Nonomura
Summary: The introduction of novel therapeutic agents has expanded the treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC). However, cross-resistance between treatments may occur, and the optimal treatment sequence must be considered.
WORLD JOURNAL OF MENS HEALTH
(2022)
Article
Medicine, General & Internal
Shabbir M. H. Alibhai, Henriette Breunis, Gregory Feng, Narhari Timilshina, Aaron Hansen, Padraig Warde, Richard Gregg, Anthony Joshua, Neil Fleshner, George Tomlinson, Urban Emmenegger
Summary: This study longitudinally examined cognitive function in older men with metastatic castration-resistant prostate cancer undergoing treatment with docetaxel, abiraterone, enzalutamide, and radium Ra 223. The findings suggest that most older men do not experience significant cognitive decline in attention, executive function, and global cognition regardless of the treatment used.
Article
Biochemistry & Molecular Biology
Arielle Shkedi, Isabelle R. Taylor, Frank Echtenkamp, Poornima Ramkumar, Mohamed Alshalalfa, Genesis M. Rivera-Marquez, Michael A. Moses, Hao Shao, Robert Jeffrey Karnes, Len Neckers, Felix Feng, Martin Kampmann, Jason E. Gestwicki
Summary: Castration-resistant prostate cancer (CRPC) is associated with increased reliance on heat shock protein 70 (HSP70) and mitochondrial chaperone protein, HSP60, is selectively required in CRPC cell lines. Knockdown of HSP60 results in loss of mitochondrial spare respiratory capacity and poor survival in prostate cancer patients.
CELL CHEMICAL BIOLOGY
(2022)
Article
Urology & Nephrology
Catherine H. Marshall, Jessa Tunacao, Varun Danda, Hua-Ling Tsai, John Barber, Rakhee Gawande, Clifford R. Weiss, Samuel R. Denmeade, Corinne Joshu
Summary: The study showed that bipolar androgen therapy (BAT) was associated with significant improvements in body composition and health indicators, but there was no correlation between improvements in lipid levels and quality of life.
Article
Cell & Tissue Engineering
Yalan Xu, Jie Mu, Zhixia Zhou, Yu Leng, Yali Yu, Xiuyue Song, Aihua Liu, Hai Zhu, Jing Li, Dong Wang
Summary: The study isolated and cultured a novel type of castration-resistant intermediate prostate stem cells that can rapidly proliferate in 2D culture dishes and be maintained for over six months. These stem cells express markers of both basal and luminal cells, and can differentiate into prostate organoids and tissues.
STEM CELL RESEARCH & THERAPY
(2022)
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
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
Ivan Henriquez, Mack I. I. I. I. I. I. Roach, Todd M. Morgan, Alberto Bossi, Junior A. Gomez, Oscar Abuchaibe, Felipe Counago
Summary: mCRPC is a complex disease with a wide range of molecular tumor behavior and high risk of progression, making early detection and treatment crucial. Treatment options have improved significantly in recent years, but clinicians find it challenging to keep up with the rapidly changing therapeutic landscape.
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
Andrei Sergeyev, Lin Gu, Amanda M. De Hoedt, Christopher L. Amling, William J. Aronson, Matthew R. Cooperberg, Christopher J. Kane, Zachary Klaassen, Martha K. Terris, Lourdes Guerrios-Rivera, Stephen J. Freedland, Ilona Csizmadi
Summary: The study found that diabetes identified by ICD-9/10 codes was associated with better overall survival in late-stage prostate cancer patients, while the "undiagnosed" diabetes identified by high HbA1c values was associated with an increase in all-cause mortality. In addition, the duration of diabetes prior to diagnosis was inversely associated with prostate cancer-specific mortality.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2023)
Review
Oncology
Thi Khanh Le, Quang Hieu Duong, Virginie Baylot, Christelle Fargette, Michael Baboudjian, Laurence Colleaux, David Taieb, Palma Rocchi
Summary: Castration-resistant prostate cancer remains a significant medical challenge, and it is important to understand the underlying mechanisms of resistance and develop new treatment approaches. This review provides an overview of the mechanisms contributing to CRPC progression and discusses current treatment options.
Review
Cell Biology
Vincenza Conteduca, Alessandra Mosca, Nicole Brighi, Ugo de Giorgi, Pasquale Rescigno
Summary: Prostate cancer is a common cancer in men and patients may develop metastatic disease after radical treatments. Prognostic biomarkers are urgently needed to define patients' risk of cancer-related death.
Review
Oncology
Fred Saad, Martin Boegemann, Kazuhiro Suzuki, Neal Shore
Summary: Nonmetastatic castration-resistant prostate cancer (nmCRPC) is characterized by rising PSA levels despite castration therapy, and patients are at risk of developing metastatic disease and cancer-related symptoms. Treatment decisions for nmCRPC patients should consider the balance between clinical benefits and potential adverse events of second-generation androgen receptor inhibitors to delay metastases and prolong survival.
PROSTATE CANCER AND PROSTATIC DISEASES
(2021)
Article
Oncology
Neal Shore, Raluca Ionescu-Ittu, Lingfeng Yang, Francois Laliberte, Malena Mahendran, Dominique Lejeune, Louise Yu, Joseph Burgents, Mei Sheng Duh, Sameer R. Ghate
Summary: This study assessed the patterns of genetic testing for homologous recombination repair mutations in patients with metastatic castration-resistant prostate cancer pre-PARP inhibitors approval. The results showed suboptimal use and access to genetic testing, with patients receiving care in an academic oncology center more likely to undergo genetic testing. Increasing the uptake rate of genetic testing in mCRPC patients is crucial to guide treatment decisions.
Article
Urology & Nephrology
Susan Halabi, Shan Jiang, Emi Terasawa, Viviana Garcia-Horton, Rajeev Ayyagari, A. Reginald Waldeck, Neal Shore
Summary: This study compared the safety and efficacy of darolutamide vs apalutamide, and darolutamide vs enzalutamide in nonmetastatic castration-resistant prostate cancer through matching-adjusted indirect comparisons. While there were no differences in metastasis-free survival, darolutamide showed lower rates of certain adverse events compared to apalutamide and enzalutamide, suggesting a more favorable safety and tolerability profile.
JOURNAL OF UROLOGY
(2021)
Article
Oncology
Neeraj Agarwal, Arun Azad, Neal D. Shore, Joan Carles, Andre P. Fay, Curtis Dunshee, Lawrence Ivan Karsh, Maria Luisa Paccagnella, Nicola Di Santo, Mohamed Elmeliegy, Xun Lin, Akos Czibere, Karim Fizazi
Summary: The TALAPRO-2 study is designed to compare the efficacy of talazoparib plus enzalutamide versus placebo plus enzalutamide as first-line treatment for mCRPC patients, with a focus on radiographic progression-free survival.
Article
Oncology
Christopher J. Sweeney, Ivor J. Percent, Sunil Babu, Jennifer L. Cultrera, Bryan A. Mehlhaff, Oscar B. Goodman, David S. Morris, Ian D. Schnadig, Costantine Albany, Neal D. Shore, Paul R. Sieber, Susan C. Guba, Wei Zhang, Volker Wacheck, Gregory P. Donoho, Anna M. Szpurka, Sophie Callies, Boris Kin Lin, Johanna C. Bendell
Summary: In patients with metastatic castration-resistant prostate cancer (mCRPC) who had progressed on abiraterone treatment, the combination of samotolisib/enzalutamide showed tolerable side effects and significantly improved progression-free survival (PFS), especially in patients with intact PTEN and no androgen receptor splice variant 7.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Andrew J. Armstrong, Arun A. Azad, Taro Iguchi, Russell Z. Szmulewitz, Daniel P. Petrylak, Jeffrey Holzbeierlein, Arnauld Villers, Antonio Alcaraz, Boris Alekseev, Neal D. Shore, Francisco Gomez-Veiga, Brad Rosbrook, Fabian Zohren, Shunsuke Yamada, Gabriel P. Haas, Arnulf Stenzl
Summary: Clinical Trial Updates provide an opportunity to disseminate additional results from studies that have already reported their primary endpoint. This study demonstrates that enzalutamide plus androgen deprivation therapy significantly prolongs survival in patients with metastatic hormone-sensitive prostate cancer, and continues to improve other secondary endpoints.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Endocrinology & Metabolism
Arnulf Stenzl, Russell Z. Szmulewitz, Daniel Petrylak, Jeffrey Holzbeierlein, Arnauld Villers, Arun Azad, Antonio Alcaraz, Boris Alekseev, Taro Iguchi, Neal D. Shore, Francisco Gomez-Veiga, Cristina Ivanescu, Brad Rosbrook, Krishnan Ramaswamy, Arijit Ganguli, Gabriel P. Haas, Andrew J. Armstrong
Summary: Enzalutamide plus ADT provides clinical benefits in defined patient subgroups versus ADT alone, while maintaining lack of pain and high HRQoL, with delayed deterioration in several HRQoL measures.
Article
Urology & Nephrology
Neal D. Shore, Arnulf Stenzl, Christopher Pieczonka, Zachary Klaassen, William J. Aronson, Lawrence Karsh, Charles J. Ryan, Jorge Ortiz, Shankar Srinivasan, Ateesha F. Mohamed, Frank Verholen
Summary: This study assessed the impact of darolutamide on urinary and bowel symptoms in patients with non-metastatic castration-resistant prostate cancer. The results showed that darolutamide significantly reduced the risk of invasive procedures and delayed the deterioration in quality of life. The safety profile of darolutamide was favorable, with similar incidence of adverse events compared to placebo.
Article
Oncology
Neal D. Shore, Alicia K. Morgans, Ghassan El-Haddad, Sandy Srinivas, Matthew Abramowitz
Summary: The diagnostic and treatment landscapes of prostate cancer are rapidly evolving and present challenges and controversies that go beyond existing guidelines. Multidisciplinary teams (MDTs) play a central role in addressing these challenges and controversies and can provide guidance on clinical decision-making in situations where novel diagnostic testing differs from established clinical risk factors. This review explores the ways in which MDTs can be utilized to address these issues throughout the prostate cancer disease continuum and mitigate disparities in care.
Article
Oncology
Emmanuel S. Antonarakis, Sumit K. Subudhi, Christopher M. Pieczonka, Lawrence I. Karsh, David I. Quinn, Jason M. Hafron, Helen M. Wilfehrt, Matthew Harmon, Nadeem A. Sheikh, Neal D. Shore, Daniel P. Petrylak
Summary: The purpose of this study was to investigate the impact of sequential or concurrent administration of androgen receptor-targeting agents (ARTAs) on sipuleucel-T immune response and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC). The results showed that the median OS remained consistent regardless of whether the agents were administered sequentially or concurrently, and sipuleucel-T induced an immunologic prime-boost effect after initial exposure, even when combined with ARTAs.
CLINICAL CANCER RESEARCH
(2023)
Review
Oncology
Neal Shore, Viviana Garcia-Horton, Emi Terasawa, Rajeev Ayyagari, Jamie Partridge Grossman, Adrianus Reginald Waldeck
Summary: Prostate cancer is a common cancer in men and initial treatments focus on reducing male hormones to control the cancer. However, some patients stop responding to these treatments and need more advanced options. Three novel therapies have become available for nonmetastatic castration-resistant prostate cancer, raising the question of how to choose the right treatment. Patient safety is crucial in treatment selection, considering the differences in safety profiles and potential harm. The selection should also consider patient preferences, clinical characteristics, and potential healthcare complications.
Article
Oncology
Maha Hussain, Bertrand Tombal, Fred Saad, Karim Fizazi, Cora N. Sternberg, E. David Crawford, Neal Shore, Evgeny Kopyltsov, Arash Rezazadeh Kalebasty, Martin Boegemann, Dingwei Ye, Felipe Cruz, Hiroyoshi Suzuki, Shivani Kapur, Shankar Srinivasan, Frank Verholen, Iris Kuss, Heikki Joensuu, Matthew R. Smith
Summary: In patients with high-volume and high-risk/low-risk metastatic hormone-sensitive prostate cancer, treatment with darolutamide improved overall survival with a similar adverse event profile in the subgroups.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Neeraj Agarwal, Fred Saad, Arun A. Azad, Joaquin Mateo, Nobuaki Matsubara, Neal D. Shore, Jayeta Chakrabarti, Hsiang-Chun Chen, Silvana Lanzalone, Alexander Niyazov, Karim Fizazi
Summary: This study describes the design and rationale of the TALAPRO-3 multinational phase III trial, comparing talazoparib plus enzalutamide versus placebo plus enzalutamide in patients with metastatic castration-sensitive prostate cancer and homologous recombination repair gene alterations. The primary endpoint is investigator-assessed radiographic progression-free survival.
Article
Oncology
Neal D. Shore, Felipe Cruz, Luke Nordquist, Laurence Belkoff, William J. Aronson, Bhupendra Tolia, Arnold Cinman, Roohollah Sharifi, Jorge Ortiz, Jacqueline Parkin, Shankar Srinivasan, Toni Sarapohja, Matthew R. Smith
Summary: For Black/African-American patients with nonmetastatic castration-resistant prostate cancer, darolutamide improved metastasis-free and overall survival, and had a favorable safety profile consistent with the overall ARAMIS population.
Article
Urology & Nephrology
Seyed Behzad Jazayeri, Lauren Folgosa Cooley, Abhishek Srivastava, Neal Shore
Summary: The treatment landscape for metastatic hormone-sensitive prostate cancer (mHSPC) has undergone significant changes. Combinatorial therapy with ADT and docetaxel or an androgen receptor pathway inhibitor has become the standard of care. Scientific evidence supports the optimization and intensification of this treatment strategy.
EUROPEAN UROLOGY OPEN SCIENCE
(2022)