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)
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
Jason Hu, Armen G. Aprikian, Ramy R. Saleh, Alice Dragomir
Summary: This descriptive study examined the utilization trends of novel hormonal agents in mCRPC patients in the early years after their approval in Quebec. The results showed an increasing proportion of patients initiating NHAs without prior chemotherapy, a shift in prescribing practices towards urologists, and a rise in ENZ users over time, indicating a change in the management of mCRPC.
Article
Medicine, Research & Experimental
Gido Snaterse, Lisanne F. van Dessel, Job van Riet, Angela E. Taylor, Michelle van der Vlugt-Daane, Paul Hamberg, Ronald de Wit, Jenny A. Visser, Wiebke Arlt, Martijn P. Lolkema, Johannes Hofland
Summary: The study revealed that 11-ketotestosterone (11KT) is the most abundant circulating active androgen in patients with CRPC, constituting 60% of the total active androgen pool. Treatment with glucocorticoids significantly reduced 11KT and testosterone concentrations. The circulating active androgen concentrations were associated with a distinct intratumor gene expression signature.
Article
Chemistry, Medicinal
Ryan L. Gonciarz, Sasank Sakhamuri, Nima Hooshdaran, Garima Kumar, Hyunjung Kim, Michael J. Evans, Adam R. Renslo
Summary: By studying models of metastatic castration-resistant prostate cancer (mCRPC), researchers found that elevated iron levels are a common feature of mCRPC. They synthesized ferrous-iron activatable drug conjugates of second and third-generation antiandrogens and found that these conjugates possessed comparable or enhanced antiproliferative activity in mCRPC cell line models. The results suggest that leveraging changes in iron metabolism may improve the tolerability and efficacy of antiandrogen therapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Oncology
Emre Yekedüz, Rana R. McKay, Silke Gillessen, Toni K. Choueiri, Yuksel Ürün
Summary: This review evaluates the impact of abiraterone acetate plus prednisone versus non-steroidal anti-androgens on overall survival for metastatic castration-sensitive prostate cancer with visceral metastasis. The analysis shows that abiraterone acetate improves overall survival in patients with visceral metastasis, while second-generation non-steroidal anti-androgens do not provide the same benefit in this population. However, both abiraterone acetate and second-generation non-steroidal anti-androgens improve overall survival in patients without visceral metastasis.
Article
Pharmacology & Pharmacy
Jean-Marc Ferrero, Hakim Mahammedi, Gwenaelle Gravis, Guilhem Roubaud, Philippe Beuzeboc, Remi Largillier, Delphine Borchiellini, Claude Linassier, Nathalie Ebran, Tanguy Pace-Loscos, Marie-Christine Etienne-Grimaldi, Renaud Schiappa, Jocelyn Gal, Gerard Milano
Summary: A study on 137 advanced prostate cancer patients treated with the first-line anti-androgen agent AA found that polymorphisms of CYP17A1, SLCO2B1, and SLCO1B3 genes were associated with AA pharmacodynamics. This suggests that host genome characteristics can help predict AA treatment efficacy and identify patients at risk for toxicity.
Article
Oncology
Samuel R. Denmeade, Hao Wang, Neeraj Agarwal, David C. Smith, Michael T. Schweizer, Mark N. Stein, Vasileios Assikis, Przemyslaw W. Twardowski, Thomas W. Flaig, Russell Z. Szmulewitz, Jeffrey M. Holzbeierlein, Ralph J. Hauke, Guru Sonpavde, Jorge A. Garcia, Arif Hussain, Oliver Sartor, Shifeng Mao, Harry Cao, Wei Fu, Ting Wang, Rehab Abdallah, Su Jin Lim, Vanessa Bolejack, Channing J. Paller, Michael A. Carducci, Mark C. Markowski, Mario A. Eisenberger, Emmanuel S. Antonarakis
Summary: Bipolar androgen therapy (BAT) shows meaningful clinical activity and safety in prostate cancer patients, suggesting it could be an effective treatment approach. The study results indicate that BAT can enhance sensitivity to enzalutamide, potentially improving survival in castration-resistant prostate cancer patients.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
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.
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
Medical Laboratory Technology
Maibritt Norgaard, Marianne T. Bjerre, Jacob Fredsoe, Soren Vang, Jorgen B. Jensen, Bram De Laere, Henrik Groenberg, Michael Borre, Johan Lindberg, Karina D. Sorensen
Summary: The clinical utility of low-pass whole-genome sequencing (LPWGS) of circulating tumor DNA (ctDNA) for prognostication in metastatic castration-resistant prostate cancer (mCRPC) was examined. The study found that high ctDNA% and high copy number alteration (CNA) burden at baseline were associated with poor treatment response, progression-free survival (PFS), and overall survival (OS). These findings were confirmed in an independent cohort.
CLINICAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Shidong Lv, Qiong Song, Guang Chen, Erdong Cheng, Wei Chen, Ryan Cole, Zeyu Wu, Laura E. Pascal, Ke Wang, Peter Wipf, Joel B. Nelson, Qiang Wei, Wenhua Huang, Zhou Wang
Summary: The study reveals differences in the mechanisms of AR nuclear localization in castration-resistant prostate cancer cells compared to traditional model, with androgen withdrawal causing only nuclear degradation rather than export, and reduced AR polyubiquitination and increased nuclear AR levels in resistant cells. The compound 3-(4-chlorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a] imidazole (CPPI) is identified as a competitive AR antagonist, blocking androgen-independent AR nuclear import and enhancing AR degradation through interaction with E3 ligase MDM2 in the nuclei of CRPC cells.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
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
Jason Hu, Armen G. Aprikian, Marie Vanhuyse, Alice Dragomir
Summary: This retrospective study compared the cardiovascular safety of abiraterone and enzalutamide in patients with metastatic castration-resistant prostate cancer. The findings suggest that abiraterone is associated with a higher risk of cardiovascular-related hospitalization, particularly for heart failure, compared to enzalutamide. The increased risk is more pronounced in patients with preexisting cardiovascular risk factors.
CLINICAL GENITOURINARY CANCER
(2022)
Article
Endocrinology & Metabolism
Min Liu, Jiaqing Yan, Kaidi Le, Ying Li, Nianzeng Xing, Guohui Li
Summary: This study evaluated the incidence and risk factors of adverse events (AEs) in patients treated with abiraterone acetate (AA) and prednisone (PDN) outside clinical trials, and their association with survival outcomes. The results showed that multiple organ metastasis, hypertension, and radiotherapy were associated with worse progression-free survival (PFS). AA was found to be effective and tolerated in real-life settings for asymptomatic or slightly symptomatic metastatic castration-resistant prostate cancer (mCRPC) patients.
FRONTIERS IN ENDOCRINOLOGY
(2023)
