Article
Endocrinology & Metabolism
John T. T. Isaacs, Susan L. L. Dalrymple, Lizamma Antony, David M. Marc Rosen, Ilsa M. M. Coleman, Peter S. S. Nelson, Maya Kostova, Iain A. A. Murray, Gary H. H. Perdew, Samuel R. R. Denmeade, Emmanuel S. S. Akinboye, W. Nathaniel Brennen
Summary: Through chemical synthesis and testing, the researchers identified ESATA-20 as a potential lead candidate for the treatment of mCRPC. It has stronger anticancer activity and fewer off-target effects compared to existing drugs.
Article
Medicine, Research & Experimental
Feng Gao, Qiaoping Xu, Zhe Tang, Nan Zhang, Yasheng Huang, Zhongyi Li, Yuliang Dai, Qiqi Yu, Jingyu Zhu
Summary: This study identified a S100A9/circMID1/miR-506-3p/MID1 axis in MDSC-Exo-regulated CRPC progression, providing new insights into the regulatory mechanisms of MDSC-Exo in CRPC progression.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
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
Biochemistry & Molecular Biology
Maria J. Orea, Javier C. Angulo, Ana Gonzalez-Corpas, David Echegaray, Marcos Marva, Maria V. T. Lobo, Begona Colas, Santiago Ropero
Summary: The development of castration-resistant prostate cancer (CRPC) is a major concern in high-risk patients after treatment for locally advanced or metastatic prostate cancer. Androgen receptor (AR) is implicated in CRPC development through its interaction with epigenetic modifier genes, highlighting the significance of epigenetic modifications. Our study reveals the epigenetic silencing of claudin-3 (CLDN3) in AR-positive CRPC cells, which is associated with DNA methylation, histone acetylation loss, and H3K27 methylation. CLDN3 expression can be restored by combined treatment with epigenetic modulators. Additionally, decreased CLDN3 expression is observed in CRPC patient samples, particularly in patients with high Gleason scores and locally advanced tumors. CLDN3 loss is also linked to worse disease-free survival and time to clinical progression, suggesting its potential as a molecular marker for prognosis and distinguishing aggressive from indolent prostate tumors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Oliver Sartor, Johann de Bono, Kim N. Chi, Karim Fizazi, Ken Herrmann, Kambiz Rahbar, Scott T. Tagawa, Luke T. Nordquist, Nitin Vaishampayan, Ghassan El-Haddad, Chandler H. Park, Tomasz M. Beer, Alison Armour, Wendy J. Perez-Contreras, Michelle DeSilvio, Euloge Kpamegan, Germo Gericke, Richard A. Messmann, Michael J. Morris, Bernd J. Krause
Summary: The radioligand therapy with Lu-177-PSMA-617 prolonged both imaging-based progression-free survival and overall survival in patients with PSMA-positive metastatic castration-resistant prostate cancer when added to standard care. Adverse events were more common with Lu-177-PSMA-617 but did not significantly impact quality of life.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Oncology
Eric Feng, Nicholas R. Rydzewski, Meng Zhang, Arian Lundberg, Matthew Bootsma, Kyle T. Helzer, Joshua M. Lang, Rahul Aggarwal, Eric J. Small, David A. Quigley, Martin Sjostrom, Shuang G. Zhao
Summary: In this study, the researchers identified the intrinsic molecular subtypes of metastatic castration-resistant prostate cancer (mCRPC) and assessed their molecular and clinical correlates using a large cohort with gene expression data. The results showed the heterogeneity of mCRPC beyond currently accepted molecular phenotypes, emphasizing the need for transcriptome-wide profiling in future studies to understand the impact of these differences on treatment responses and outcomes.
CLINICAL CANCER RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Hsin-Chih Yeh, Chia-Cheng Su, Yen-Hsuan Wu, Cheng Hsueh Lee, Bo-Ying Bao, Wei-Chung Cheng, Shu-Chi Wang, Po-Len Liu, Chien-Chih Chiu, Chih-Pin Chuu, Chien-Chih Ke, Hsin-En Wu, Yuan-Ru Chen, Wei-Ju Chung, Shu-Pin Huang, Chia-Yang Li
Summary: This study found that 3-BP effectively inhibits growth and motility of prostate cancer cells, particularly castration-resistant prostate cancer (CRPC) cells. Additionally, 3-BP attenuates tumor growth in a xenograft murine model and significantly regulates the cell cycle pathway. Therefore, 3-BP shows promise as a potential drug for treating CRPC.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Yasemin Sanli, Duygu Has Simsek, Oner Sanli, Rathan M. Subramaniam, Ayse Tuba Kendi
Summary: Lu-177-PSMA therapy shows promising clinical efficacy in patients with mCRPC, with predictors of efficacy being significant. Ongoing clinical trials, including a phase III multicenter FDA registration trial, are currently being conducted in the United States.
Article
Oncology
Moloud A. Sooreshjani, Kumar Nikhil, Mohini Kamra, Dung N. Nguyen, Dinesh Kumar, Kavita Shah
Summary: Prostate cancer is the leading cause of cancer-related death in men, with most patients progressing to castration-resistant prostate cancer (CRPC) which currently has no cure. The study identified LIMK2 as a key player in CRPC and its negative regulation of NKX3.1, a prostate-specific tumor suppressor. Inhibiting LIMK2 to rescue NKX3.1 loss presents a promising therapeutic strategy for preventing and delaying prostate cancer progression, by co-targeting driver pathways such as AR, ARv7, and AKT signaling.
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)
Editorial Material
Oncology
Haider Al-Janabi, Claire E. Lewis
Summary: Androgen deprivation therapy (ADT) is a frontline treatment for early and metastatic prostate cancer, but tumor resistance to ADT can lead to major clinical consequences. Tumor-associated macrophages have been shown to drive tumor resistance to various anticancer therapies, and researchers have now identified a novel mechanism involving the transfer of cholesterol from macrophages to cancer cells during ADT, which activates androgen receptors and promotes tumor resistance.
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
Kim N. Chi, Dana Rathkopf, Matthew R. Smith, Eleni Efstathiou, Gerhardt Attard, David Olmos, Ji Youl Lee, Eric J. Small, Andrea J. Pereira De Santana Gomes, Guilhem Roubaud, Marniza Saad, Bogdan Zurawski, Valerii Sakalo, Gary E. Mason, Peter Francis, George Wang Ms, Daphne Wu, Brooke Diorio, Angela Lopez-Gitlitz, Shahneen Sandhu
Summary: This study investigated the efficacy of niraparib in combination with abiraterone acetate plus prednisone in patients with mCRPC and HRR gene alterations. The results showed that the combination therapy significantly prolonged radiographic progression-free survival compared to abiraterone acetate plus prednisone alone. The treatment was well tolerated with manageable adverse events.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Thomas Powles, Kobe C. Yuen, Silke Gillessen, Edward E. Kadel, Dana Rathkopf, Nobuaki Matsubara, Charles G. Drake, Karim Fizazi, Josep M. Piulats, Piotr J. Wysocki, Gary L. Buchschacher, Boris Alekseev, Begona Mellado, Boguslawa Karaszewska, Jennifer F. Doss, Grozdana Rasuo, Asim Datye, Sanjeev Mariathasan, Patrick Williams, Christopher J. Sweeney
Summary: Early clinical data suggest that some patients with castration-resistant prostate cancer may benefit from PD-L1 inhibition, especially with enzalutamide. However, a trial combining atezolizumab with enzalutamide did not improve overall survival in unselected patients. Genomic and immune biomarkers associated with response to immune checkpoint inhibitors were identified.
Article
Endocrinology & Metabolism
Xi Chen, Junjie Ma, Xin'an Wang, Tong Zi, Duocheng Qian, Chao Li, Chengdang Xu
Summary: This study identified nine genes associated with vinblastine resistance and verified the crucial role of CCNB1 and AURKA in castration-resistant prostate cancer (CRPC) resistance to vinblastine. These genes also influenced the progression of prostate cancer (PCa).
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Urology & Nephrology
Hannah L. Rhodes, Laura Yarram-Smith, Sarah J. Rice, Ayla Tabaksert, Noel Edwards, Alice Hartley, Mark N. Woodward, Sarah L. Smithson, Charles Tomson, Gavin I. Welsh, Margaret Williams, David T. Thwaites, John A. Sayer, Richard J. M. Coward
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2015)
Article
Oncology
C. J. Morrow, F. Trapani, R. L. Metcalf, G. Bertolini, C. L. Hodgkinson, G. Khandelwal, P. Kelly, M. Galvin, L. Carter, K. L. Simpson, S. Williamson, C. Wirth, N. Simms, L. Frankliln, K. K. Frese, D. G. Rothwell, D. Nonaka, C. J. Miller, G. Brady, F. H. Blackhall, C. Dive
ANNALS OF ONCOLOGY
(2016)
Article
Surgery
S. Tadiparthi, A. Hartley, L. Alzweri, M. Mecci, H. Siddiqui
JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY
(2016)
Article
Multidisciplinary Sciences
Stuart C. Williamson, Robert L. Metcalf, Francesca Trapani, Sumitra Mohan, Jenny Antonello, Benjamin Abbott, Hui Sun Leong, Christopher P. E. Chester, Nicole Simms, Radoslaw Polanski, Daisuke Nonaka, Lynsey Priest, Alberto Fusi, Fredrika Carlsson, Anders Carlsson, Mary J. C. Hendrix, Richard E. B. Seftor, Elisabeth A. Seftor, Dominic G. Rothwell, Andrew Hughes, James Hicks, Crispin Miller, Peter Kuhn, Ged Brady, Kathryn L. Simpson, Fiona H. Blackhall, Caroline Dive
NATURE COMMUNICATIONS
(2016)
Article
Mathematical & Computational Biology
Nicola Lazzarini, Pawel Widera, Stuart Williamson, Rakesh Heer, Natalio Krasnogor, Jaume Bacardit
Article
Cell Biology
Mohammad Moad, Edouard Hannezo, Simon J. Buczacki, Laura Wilson, Amira El-Sherif, David Sims, Robert Pickard, Nicholas A. Wright, Stuart C. Williamson, Doug M. Turnbull, Robert W. Taylor, Laura Greaves, Craig N. Robson, Benjamin D. Simons, Rakesh Heer
Article
Biochemistry & Molecular Biology
Daniel J. O'Neill, Stuart Charles Williamson, Dhuha Alkharaif, Isabella Christina Mazzaro Monteiro, Marilyn Goudreault, Luke Gaughan, Craig N. Robson, Anne-Claude Gingras, Olivier Binda
Article
Oncology
Sandra Cristea, Garry L. Coles, Daniel Hornburg, Maya Gershkovitz, Julia Arand, Siqi Cao, Triparna Sen, Stuart C. Williamson, Jun W. Kim, Alexandros P. Drainas, Andrew He, Laurent Le Cam, Lauren Averett Byers, Michael P. Snyder, Kevin Contrepois, Julien Sage
Letter
Oncology
Francesca Bizzaro, Ilaria Fuso Nerini, Molly A. Taylor, Alessia Anastasia, Massimo Russo, Giovanna Damia, Federica Guffanti, Francesca Guana, Paola Ostano, Lucia Minoli, Maureen M. Hattersley, Stephanie Arnold, Antonio Ramos-Montoya, Stuart C. Williamson, Alessandro Galbiati, Jelena Urosevic, Elisabetta Leo, Ugo Cavallaro, Carmen Ghilardi, Simon T. Barry, Maria Rosa Bani, Raffaella Giavazzi
Summary: The combination therapy of PARP inhibitors and VEGF-signalling inhibitors in ovarian cancer has shown broad anti-tumor activity and prolonged survival, regardless of the tumor's homologous recombination repair status. The mechanisms of action of olaparib and cediranib act through complementary mechanisms affecting tumor cells and tumor microenvironment, respectively, suggesting no dominant common mechanistic inter-dependency driving therapeutic benefit.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Oncology
Sarah M. Pearsall, Stuart C. Williamson, Sam Humphrey, Ellyn Hughes, Derrick Morgan, Fernando J. Garcia Marques, Griselda Awanis, Rebecca Carroll, Laura Burks, Yan Ting Shue, Abel Bermudez, Kristopher K. Frese, Melanie Galvin, Mathew Carter, Lynsey Priest, Alastair Kerr, Cong Zhou, Trudy G. Oliver, Jonathan D. Humphries, Martin J. Humphries, Fiona Blackhall, Ian G. Cannell, Sharon J. Pitteri, Gregory J. Hannon, Julien Sage, Caroline Dive, Kathryn L. Simpson
Summary: This study investigates the phenotype and molecular mechanisms of vasculogenic mimicry (VM) in small cell lung cancer (SCLC) using circulating tumor cell-derived explant (CDX) models and genetically engineered mouse models (GEMMs). The results show that VM vessels are present in CDX models, GEMMs, and SCLC patient biopsies, and perfused VM vessels support tumor growth. Only NOTCH-active non-NE cells are VM-competent and exhibit characteristics related to blood vessel development and extracellular matrix organization. On Matrigel, VM-primed non-NE cells remodel the extracellular matrix into hollow tubules through an integrin b1-dependent process.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Article
Oncology
Lorna Hopcroft, Eleanor M. M. Wigmore, Stuart C. C. Williamson, Susana Ros, Cath Eberlein, Jennifer I. Moss, Jelena Urosevic, Larissa S. Carnevalli, Sara Talbot, Lauren Bradshaw, Catherine Blaker, Sreeharsha Gunda, Venetia Owenson, Scott Hoffman, Daniel Sutton, Stewart Jones, Richard J. A. Goodwin, Brandon S. Willis, Claire Rooney, Elza DeBruin, Simon T. Barry
Summary: Combining AKT inhibitor and SERD improved PFS in a clinical trial for HR+ breast cancer patients. However, CDK4/6 inhibitor treatment may reduce response to subsequent endocrine treatment. This study explored the impact of CDK4/6 inhibitor treatment on breast tumor cell function and response to fulvestrant and capivasertib.
Correction
Oncology
Lorna Hopcroft, Eleanor M. Wigmore, Stuart C. Williamson, Susana Ros, Cath Eberlein, Jennifer I. Moss, Jelena Urosevic, Larissa S. Carnevalli, Sara Talbot, Lauren Bradshaw, Catherine Blaker, Sreeharsha Gunda, Venetia Owenson, Scott Hoffmann, Daniel Sutton, Stewart Jones, Richard J. A. Goodwin, Brandon S. Willis, Claire Rooney, Elza C. de Bruin, Simon T. Barry
Correction
Oncology
Lorna Hopcroft, Eleanor M. M. Wigmore, Stuart C. C. Williamson, Susana Ros, Cath Eberlein, Jennifer I. I. Moss, Jelena Urosevic, Larissa S. S. Carnevalli, Sara Talbot, Lauren Bradshaw, Catherine Blaker, Sreeharsha Gunda, Venetia Owenson, Scott Hoffmann, Daniel Sutton, Stewart Jones, Richard J. A. Goodwin, Brandon S. S. Willis, Claire Rooney, Elza DeBruin, Simon T. T. Barry