Article
Biochemistry & Molecular Biology
Levi Groen, Iris Kloots, David Englert, Kelly Seto, Lana Estafanos, Paul Smith, Gerald W. Verhaegh, Niven Mehra, Jack A. Schalken
Summary: The clinical utility of circulating tumor cells (CTC) as a non-invasive multipurpose biomarker is well recognized. The earliest methods for enriching CTCs relied on antibody-based positive selection, but it has limitations in capturing the heterogeneity of cancer. This study used the recently FDA-approved Parsortix (R) technology to enrich CTCs from prostate cancer patients and found that targeted CTC transcriptome profiling may be predictive of therapy response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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.
Article
Biochemistry & Molecular Biology
Khrystany T. Isebia, Martijn P. Lolkema, Guido Jenster, Ronald de Wit, John W. M. Martens, Job van Riet
Summary: This study found that in metastatic castration-resistant prostate cancer, in addition to AR-V7, AR45 and AR-V3 were also commonly seen AR splice variants. The presence of any AR-Vs may be associated with higher AR expression. These AR-Vs could potentially serve as predictive and prognostic biomarkers in metastatic castration-resistant prostate cancer, similar or complementary to AR-V7.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Frantzeska Giginis, Joshua Wang, Aaron Chavez, Manuela Martins-Green
Summary: Prostate Cancer (PCa) is the second most prevalent cancer in the world. Currently, most treatments for PCa involve Androgen Deprivation Therapy (ADT) which is not effective for metastatic Castration-Resistant Prostate Cancer (mCRPC). Decreasing the enzyme catalase, which reduces oxidative stress levels, has the potential to provide another target for Prostate Cancer therapy.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Review
Urology & Nephrology
Soum D. Lokeshwar, Zachary Klaassen, Fred Saad
Summary: Metastatic prostate cancer is associated with high morbidity and mortality rates. Treatment of non-metastatic prostate cancer often involves androgen deprivation therapy (ADT), but many patients eventually develop castration-resistant prostate cancer (CRPC). A new stage called non-metastatic CRPC (nmCRPC) has gained attention, with three novel nonsteroidal antiandrogens (enzalutamide, apalutamide, darolutamide) showing promising results in clinical trials.
NATURE REVIEWS UROLOGY
(2021)
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)
Review
Pharmacology & Pharmacy
Maoping Cai, Xian-Lu Song, Xin-An Li, Mingkun Chen, Jiading Guo, Dong Hua Yang, Zhanghui Chen, Shan-Chao Zhao
Summary: Castration-resistant prostate cancer (CRPC), especially metastatic CRPC (mCRPC), is a common and deadly malignancy in men worldwide. The natural or acquired drug resistance of CRPC makes clinical treatment challenging. Understanding the mechanisms of drug resistance in mCRPC is essential for developing effective therapeutic strategies. This review focuses on new insights in mCRPC treatment and discusses the mechanisms governing resistance to new drugs, such as taxanes, androgen receptor signaling inhibitors (ARSIs), and poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). Strategies to overcome drug resistance based on these mechanisms are also discussed.
DRUG RESISTANCE UPDATES
(2023)
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
Oncology
Fen Ma, Seiji Arai, Keshan Wang, Carla Calagua, Amanda R. Yuan, Larysa Poluben, Zhongkai Gu, Joshua W. Russo, David J. Einstein, Huihui Ye, Meng Xiao He, Yu Liu, Eliezer Van Allen, Adam G. Sowalsky, Manoj K. Bhasin, Xin Yuan, Steven P. Balk
Summary: This study reveals the importance of Wnt/beta-catenin signaling in prostate cancer, showing its role in stem cell maintenance and invasion. It identifies new effectors and drivers of this pathway in prostate cancer, such as ROR1 and APC genomic loss. The findings suggest that targeting Wnt/beta-catenin signaling may be a potential therapeutic strategy for prostate cancer.
Article
Oncology
Denis Maillet, Nathalie Allioli, Julien Peron, Adriana Plesa, Myriam Decaussin-Petrucci, Sophie Tartas, Christophe Sajous, Alain Ruffion, Sebastien Crouzet, Gilles Freyer, Virginie Vlaeminck-Guillem
Summary: Although controversial, HER2 can be overexpressed in prostate cancer progression. This study found that HER2 expression in circulating tumor cells (CTCs) of patients with metastatic castration-resistant prostate cancer (mCRPC) was associated with poor long-term clinical outcomes. HER2 expression was also linked to shorter PSA-PFS, radiological-PFS, and OS, suggesting potential prognostic value and therapeutic implications for targeting the HER2 pathway in mCRPC patients.
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.
Article
Oncology
Khrystany T. Isebia, Eshwari Dathathri, Noortje Verschoor, Afroditi Nanou, Anouk C. De Jong, Frank A. W. Coumans, Leon W. M. M. Terstappen, Jaco Kraan, John W. M. Martens, Ruchi Bansal, Martijn P. Lolkema
Summary: This study compared the composition of circulating tumor cells (CTCs) and tumor-derived extracellular vesicles (tdEVs) in the blood of patients with metastatic castration-naive prostate cancer (CNPC) and metastatic castration-resistant prostate cancer (CRPC). The study found potential differences between these biomarkers in the two disease stages, with lower CTC and tdEV levels in CNPC compared to CRPC patients. Furthermore, the study observed a decline in CTC/tdEV numbers 6 months after androgen deprivation therapy (ADT).
Article
Medicine, General & Internal
Blossom Mak, Hui-Ming Lin, Edmond M. Kwan, Heidi Fettke, Ben Tran, Ian D. Davis, Kate Mahon, Martin R. Stockler, Karen Briscoe, Gavin Marx, Alison Zhang, Megan Crumbaker, Winston Tan, Kevin Huynh, Thomas G. Meikle, Natalie A. Mellett, Andrew J. Hoy, Pan Du, Jianjun Yu, Shidong Jia, Anthony M. Joshua, David J. Waugh, Lisa M. Butler, Manish Kohli, Peter J. Meikle, Arun A. Azad, Lisa G. Horvath
Summary: This study assessed the association between circulating lipids, somatic genetic aberrations, and clinical outcomes in men with metastatic castration-resistant prostate cancer (mCRPC). The results revealed that certain genetic aberrations were associated with elevated circulating sphingolipids, and patients with both genetic and lipid abnormalities had worse prognosis. These findings may have implications for the selection of metabolic therapies.
Review
Oncology
Neeraj Agarwal, Tian Zhang, Eleni Efstathiou, Nicolas Sayegh, Arne Engelsberg, Fred Saad, Karim Fizazi
Summary: For about a decade, poly [ADP ribose] polymerases (PARP) inhibitors have been primarily used for treating tumors with deficiencies in the BRCA genes. However, in advanced prostate cancer driven by the androgen receptor (AR), there is growing evidence of an interaction between AR and PARP that can be therapeutically targeted regardless of the tumor's DNA homologous recombination repair (HRR) machinery. Clinical trials have shown increased anti-tumor activity in metastatic prostate cancer patients when combining PARP inhibitors with AR pathway inhibitors, regardless of HRR gene alterations.
EUROPEAN JOURNAL OF CANCER
(2023)
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.
Review
Biochemistry & Molecular Biology
Orit Rozenblatt-Rosen, Aviv Regev, Philipp Oberdoerffer, Tal Nawy, Anna Hupalowska, Jennifer E. Rood, Orr Ashenberg, Ethan Cerami, Robert J. Coffey, Emek Demir, Li Ding, Edward D. Esplin, James M. Ford, Jeremy Goecks, Sharmistha Ghosh, Joe W. Gray, Justin Guinney, Sean E. Hanlon, Shannon K. Hughes, E. Shelley Hwang, Christine A. Iacobuzio-Donahue, Judit Jane-Valbuena, Bruce E. Johnson, Ken S. Lau, Tracy Lively, Sarah A. Mazzilli, Dana Pe'er, Sandro Santagata, Alex K. Shalek, Denis Schapiro, Michael P. Snyder, Peter K. Sorger, Avrum E. Spira, Sudhir Srivastava, Kai Tan, Robert B. West, Elizabeth H. Williams
Article
Multidisciplinary Sciences
Joshi J. Alumkal, Duanchen Sun, Eric Lu, Tomasz M. Beer, George V. Thomas, Emile Latour, Rahul Aggarwal, Jeremy Cetnar, Charles J. Ryan, Shaadi Tabatabaei, Shawna Bailey, Claire B. Turina, David A. Quigley, Xiangnan Guan, Adam Foye, Jack F. Youngren, Joshua Urrutia, Jiaoti Huang, Alana S. Weinstein, Verena Friedl, Matthew Rettig, Robert E. Reiter, Daniel E. Spratt, Martin Gleave, Christopher P. Evans, Joshua M. Stuart, Yiyi Chen, Felix Y. Feng, Eric J. Small, Owen N. Witte, Zheng Xia
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Oncology
Xiangnan Guan, Duanchen Sun, Eric Lu, Joshua A. Urrutia, Robert Evan Reiter, Matthew Rettig, Christopher P. Evans, Primo Lara, Martin Gleave, Tomasz M. Beer, George Thomas, Jiaoti Huang, Rahul R. Aggarwal, David A. Quigley, Adam Foye, William S. Chen, Jack Youngren, Alana S. Weinstein, Joshua M. Stuart, Felix Y. Feng, Eric J. Small, Zheng Xia, Joshi J. Alumkal
CLINICAL CANCER RESEARCH
(2020)
Article
Genetics & Heredity
Shuang G. Zhao, William S. Chen, Haolong Li, Adam Foye, Meng Zhang, Martin Sjostrom, Rahul Aggarwal, Denise Playdle, Arnold Liao, Joshi J. Alumkal, Rajdeep Das, Jonathan Chou, Junjie T. Hua, Travis J. Barnard, Adina M. Bailey, Eric D. Chow, Marc D. Perry, Ha X. Dang, Rendong Yang, Ruhollah Moussavi-Baygi, Li Zhang, Mohammed Alshalalfa, S. Laura Chang, Kathleen E. Houlahan, Yu-Jia Shiah, Tomasz M. Beer, George Thomas, Kim N. Chi, Martin Gleave, Amina Zoubeidi, Robert E. Reiter, Matthew B. Rettig, Owen Witte, M. Yvonne Kim, Lawrence Fong, Daniel E. Spratt, Todd M. Morgan, Rohit Bose, Franklin W. Huang, Hui Li, Lisa Chesner, Tanushree Shenoy, Hani Goodarzi, Irfan A. Asangani, Shahneen Sandhu, Joshua M. Lang, Nupam P. Mahajan, Primo N. Lara, Christopher P. Evans, Phillip Febbo, Serafim Batzoglou, Karen E. Knudsen, Housheng H. He, Jiaoti Huang, Wilbert Zwart, Joseph F. Costello, Jianhua Luo, Scott A. Tomlins, Alexander W. Wyatt, Scott M. Dehm, Alan Ashworth, Luke A. Gilbert, Paul C. Boutros, Kyle Farh, Arul M. Chinnaiyan, Christopher A. Maher, Eric J. Small, David A. Quigley, Felix Y. Feng
Article
Oncology
Shinji Iizuka, Manuela Quintavalle, Jose C. Navarro, Kyle P. Gribbin, Robert J. Ardecky, Matthew M. Abelman, Chen-Ting Ma, Eduard Sergienko, Fu-Yue Zeng, Ian Pass, George Thomas, Shannon K. McWeeney, Christian A. Hassig, Anthony B. Pinkerton, Sara A. Courtneidge
Summary: In this study, TAO3 was identified as a key regulator of invadopodia formation and function through high-content screening, highlighting its potential as a therapeutic target for invasive cancers.
Article
Oncology
Allen Li, Jamie M. Keck, Swapnil Parmar, Janice Patterson, Marilyne Labrie, Allison L. Creason, Brett E. Johnson, Molly Downey, George Thomas, Carol Beadling, Laura M. Heiser, Annette Kolodzie, Alexander R. Guimaraes, Christopher L. Corless, Joe W. Gray, Gordon B. Mills, Raymond C. Bergan, Zahi I. Mitri
Summary: The study describes an integrative approach to understanding the clinical significance of heterogeneity in breast cancer between metastatic lesions using multi-omic analyses of serial biopsies, aiming to improve cancer management. The researchers found remarkable heterogeneity among metastatic lesions in patients with metastatic breast cancer, resulting in discordance in receptor status and genomic alterations and mixed treatment responses.
NPJ PRECISION ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Sebnem Ece Eksi, Alex Chitsazan, Zeynep Sayar, George Thomas, Andrew J. Fields, Ryan P. Kopp, Paul T. Spellman, Andrew C. Adey
Summary: High tumor heterogeneity makes it difficult to identify molecular subtypes in prostate cancer. Here, the authors integrate single-cell chromatin accessibility data with multiplex imaging to reveal distinct chromatin features and transcription factor binding signatures in high- and low-grade prostate tumors.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Xiangnan Guan, Fanny Polesso, Chaojie Wang, Archana Sehrawat, Reed M. Hawkins, Susan E. Murray, George Thomas, Breanna Caruso, Reid F. Thompson, Mary A. Wood, Christina Hipfinger, Scott A. Hammond, Julie N. Graff, Zheng Xia, Amy E. Moran
Summary: Immune checkpoint blockade has revolutionized oncology by inducing durable anti-tumour immunity. In advanced prostate cancer patients, immunotherapy treatments have largely failed. However, inhibiting androgen receptor activity can increase the sensitivity of tumor-bearing hosts to checkpoint blockade therapy by enhancing CD8 T cell function and improving responsiveness to PD-1 targeted therapy.
Article
Biochemical Research Methods
Andikan J. Nwosu, Santosh A. Misal, Thy Truong, Richard H. Carson, Kei G. Webber, Nathaniel B. Axtell, Yiran Liang, S. Madisyn Johnston, Kenneth L. Virgin, Ethan G. Smith, George Thomas, Terry Morgan, John C. Price, Ryan T. Kelly
Summary: This study modified a sample processing workflow to extract proteins from FFPE tissues and analyze protein expression. By optimizing the extraction conditions, a high-confidence proteome was obtained, and the protein coverage for FFPE tissues reached 88% compared to frozen tissues.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Oncology
Martin Sjostrom, Shuang G. Zhao, Samuel Levy, Meng Zhang, Yuhong Ning, Raunak Shrestha, Arian Lundberg, Cameron Herberts, Adam Foye, Rahul Aggarwal, Junjie T. Hua, Haolong Li, Anna Bergamaschi, Corinne Maurice-Dror, Ashutosh Maheshwari, Sujun Chen, Sarah W. S. Ng, Wenbin Ye, Jessica Petricca, Michael Fraser, Lisa Chesner, Marc D. Perry, Thaidy Moreno-Rodriguez, William S. Chen, Joshi J. Alumkal, Jonathan Chou, Alicia K. Morgans, Tomasz M. Beer, George Thomas, Martin Gleave, Paul Lloyd, Tierney Phillips, Erin McCarthy, Michael C. Haffner, Amina Zoubeidi, Matti Annala, Robert E. Reiter, Matthew B. Rettig, Owen N. Witte, Lawrence Fong, Rohit Bose, Franklin W. Huang, Jianhua Luo, Anders Bjartell, Joshua M. Lang, Nupam P. Mahajan, Primo N. Lara, Christopher P. Evans, Phuoc T. Tran, Edwin M. Posadas, Chuan He, Xiao-Long Cui, Jiaoti Huang, Wilbert Zwart, Luke A. Gilbert, Christopher A. Maher, Paul C. Boutros, Kim N. Chi, Alan Ashworth, Eric J. Small, Housheng H. He, Alexander W. Wyatt, David A. Quigley, Felix Y. Feng
Summary: This study integrates whole-genome 5hmC, DNA, 5mC, and transcriptome sequencing to investigate prostate cancer. The results show that 5hmC marks activation of cancer drivers and downstream targets, and reveal altered cell states throughout the disease course. Additionally, 5hmC sequencing of cell-free DNA proves useful as a prognostic biomarker for identifying an aggressive subtype of prostate cancer.
Article
Multidisciplinary Sciences
Thomas C. Westbrook, Xiangnan Guan, Eva Rodansky, Diana Flores, Chia Jen Liu, Aaron M. Udager, Radhika A. Patel, Michael C. Haffner, Ya-Mei Hu, Duanchen Sun, Tomasz M. Beer, Adam Foye, Rahul Aggarwal, David A. Quigley, Jack F. Youngren, Charles J. Ryan, Martin Gleave, Yuzhuo Wang, Jiaoti Huang, Ilsa Coleman, Colm Morrissey, Peter S. Nelson, Christopher P. Evans, Primo Lara, Robert E. Reiter, Owen Witte, Matthew Rettig, Christopher K. Wong, Alana S. Weinstein, Vlado Uzunangelov, Josh M. Stuart, George Thomas, Felix Y. Feng, Eric J. Small, Joel A. Yates, Zheng Xia, Joshi J. Alumkal
Summary: This study analyzed the transcriptomes of patient tumor biopsies before and during enzalutamide treatment, and identified a gene expression program associated with lineage plasticity risk and poor outcomes. The findings suggest that tumors harboring this gene expression program may be at particular risk for resistance mediated by lineage plasticity.
NATURE COMMUNICATIONS
(2022)
Meeting Abstract
Oncology
Thomas Westbrook, Xiangnan Guan, Aaron M. Udager, Michael Haffner, Tomasz M. Beer, Rahul Raj Aggarwal, Charles J. Ryan, Martin Gleave, Jiaoti Huang, Christopher P. Evans, Robert Evan Reiter, Owen Witte, Matthew Rettig, Josh Stuart, George V. Thomas, Felix Y. Feng, Eric Jay Small, Joel Yates, Zheng Xia, Joshi J. Alumkal
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Alison R. Miller, Daniel Krasnonosenkikh, Monica Thanawala, Kai Chih Huang, George V. Thomas, Alexandra B. Lantermann, Hongyue Dai, Masoud Sadaghiani, John A. Wagner, Pearl Huang
MOLECULAR CANCER THERAPEUTICS
(2021)
Meeting Abstract
Oncology
Ben L. Kong, Brett E. Johnson, Jamie M. Keck, Souraya Mitri, Patrick Leyshock, Jayne M. Stommel, Kiara Siex, Marlana Klinger, Christina L. Zheng, Rochelle Williams-Belizaire, Shannon McWeeney, Jeremy Goecks, Annette Kolodzie, Alexander R. Guimaraes, George V. Thomas, Christopher L. Corless, Zahi I. Mitri, Joe W. Gray, Gordon B. Mills, Raymond C. Bergan
Article
Cell Biology
Hui-wen Lue, Daniel S. Derrick, Soumya Rao, Ahna Van Gaest, Larry Cheng, Jennifer Podolak, Samantha Lawson, Changhui Xue, Devin Garg, Ralph I. I. I. I. I. I. White, Christopher W. Ryan, Justin M. Drake, Anna Ritz, Laura M. Heiser, George Thomas
Summary: The combination therapy of cabozantinib and dasatinib shows promising efficacy in treating advanced NCCRCC by synergistically reducing cell viability through downregulation of the MAPK-ERK signaling pathway, leading to tumor regression. Additionally, the addition of a MEK inhibitor enhances the efficacy of the combination treatment.
CELL REPORTS MEDICINE
(2021)