Article
Medicine, General & Internal
Xiaojian Qin, Dongmei Ji, Weijie Gu, Weiqing Han, Hong Luo, Chuanjun Du, Qing Zou, Zhongquan Sun, Chaohong He, Shaoxing Zhu, Tie Chong, Xin Yao, Ben Wan, Xinfeng Yang, Aobing Bai, Chunlei Jin, Jianjun Zou, Dingwei Ye
Summary: This study evaluated the safety, pharmacokinetics, and activity of the novel AR antagonist SHR3680 in patients with metastatic CRPC. The results showed that SHR3680 was well tolerated and had promising anti-tumor activity across all doses. A daily dose of 240 mg was recommended for further phase 3 study.
Article
Oncology
Anthony Serritella, Daniel Shevrin, Elisabeth Heath, James L. Wade, Elia Martinez, Amanda Anderson, Joseph Schonhoft, Yen-Lin Chu, Theodore Karrison, Walter M. Stadler, Russell Z. Szmulewitz
Summary: This study evaluated the effectiveness of dual androgen receptor (AR) and glucocorticoid receptor (GR) antagonism in castration-resistant prostate cancer (CRPC). The combination of enzalutamide and mifepristone was found to be safe and well-tolerated, but did not meet the primary endpoint. Further research should explore the use of more specific GR antagonists combined with AR antagonists in earlier disease stages.
CLINICAL CANCER RESEARCH
(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
Oncology
Mark N. Stein, Lawrence Fong, Ronald Tutrone, Anthony Mega, Elaine T. Lam, Megan Parsi, Surya Vangala, Andres A. Gutierrez, Naomi B. Haas
Summary: The combination of ADXS31-142 and pembrolizumab shows promise in the treatment of metastatic castration-resistant prostate cancer, with good safety and tolerability.
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)
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.
Review
Medicine, General & Internal
Tianyi Zhou, Qin Feng
Summary: Prostate cancer is a major cause of cancer death, affecting millions of men worldwide. The progression to castration-resistant prostate cancer (CRPC) is associated with dependence on androgen receptor (AR) signaling, which involves various transcription factors. Understanding the role of transcription factors in CRPC could lead to new therapeutic targets for treatment.
FRONTIERS IN MEDICINE
(2022)
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
Urology & Nephrology
Linda K. Rushworth, Carolyn Loveridge, Mark Salji, Martin MacLeod, Ernest Mui, David Sumpton, Matthew Neilson, Ann Hedley, Laura Alexander, Elaine McCartney, Rachana Patel, Jan Wallace, Christian Delles, Rob Jones, Hing Y. Leung
Summary: The SPECTRE study provides evidence that statins may have a therapeutic effect on CRPC, with early signs of disease stabilization. Metabolomics analysis suggests that altered tryptophan metabolism may be associated with the tumor response to statins.
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
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
Oncology
Vadim S. Koshkin, Nicholas Henderson, Marihella James, Divya Natesan, Dory Freeman, Amanda Nizam, Christopher T. Su, Ali Raza Khaki, Chelsea K. Osterman, Michael J. Glover, Ryan Chiang, Dimitrios Makrakis, Rafee Talukder, Emily Lemke, T. Anders Olsen, Jayanshu Jain, Albert Jang, Alicia Ali, Tanya Jindal, Jonathan Chou, Terence W. Friedlander, Christopher Hoimes, Arnab Basu, Yousef Zakharia, Pedro C. Barata, Mehmet A. Bilen, Hamid Emamekhoo, Nancy B. Davis, Sumit A. Shah, Matthew I. Milowsky, Shilpa Gupta, Matthew T. Campbell, Petros Grivas, Guru P. Sonpavde, Deepak Kilari, Ajjai S. Alva
Summary: Enfortumab vedotin has shown consistent responses in a large retrospective cohort, including patients with variant histology, FGFR3 alterations, and previously excluded patients with comorbidities and low estimated glomerular filtration rates. The drug has been effective in treating a wide range of patient populations, replicating previously reported clinical trial data in a real-world setting.
Article
Oncology
Tanya Jindal, Jonathan Chou, Terence Friedlander, Pedro C. Barata, Vadim S. Koshkin
Summary: This study aimed to investigate the efficacy of ICI treatment in aUC patients who previously progressed on another ICI regimen. The results showed limited effectiveness of ICI treatment in patients who had progression on another ICI regimen.
CLINICAL GENITOURINARY CANCER
(2022)
Article
Oncology
Albert Jang, Ellen B. Jaeger, Elisa M. Ledet, John Xie, Brian E. Lewis, Jodi L. Layton, Oliver Sartor, Pedro C. Barata, Christopher R. Trevino
Summary: This study found that prostate cancer rarely spreads to the central nervous system. Out of 579 patients with extracranial metastatic prostate cancer, 12 patients were identified to have CNS metastases based on imaging, including six patients with brain metastases. There was no statistically significant difference in survival between patients with CNS metastases and those without after the development of extracranial metastases.
CLINICAL GENITOURINARY CANCER
(2023)
Article
Oncology
Akram M. Shayeb, Hannah Dzimitrowicz McManus, Danielle Urman, Chinmay Jani, Tian Zhang, Nazli Dizman, Luis Meza, Akhilesh Sivakumar, Chun L. Gan, Pedro Barata, Mehmet A. Bilen, Xin Gao, Daniel Heng, Sumanta Pal, Ravi Narra, Deepak Kilari, Marina D. Kaymakcalan, Bradley McGregor, Toni K. Choueiri, Rana R. McKay
Summary: In this retrospective multicenter study, the safety of cabozantinib with different anticoagulants in patients with advanced RCC was investigated. The study found that DOACs appear to be safe for VTE treatment in patients on cabozantinib without increasing the risk of major bleeding events. Optimized anticoagulation management remains vital in clinical practice.
CLINICAL GENITOURINARY CANCER
(2023)
Article
Oncology
Justin Swaby, Ankita Aggarwal, Akshee Batra, Anubhav Jain, Lakshya Seth, Nickolas Stabellini, Marcio Sommer Bittencourt, Darryl Leong, Zachary Klaassen, Pedro Barata, Nicolas Sayegh, Neeraj Agarwal, Martha Terris, Avirup Guha
Summary: An updated meta-analysis reveals that androgen deprivation therapy (ADT) is not associated with the development of metabolic syndrome (MetS) and the association with diabetes is weaker than previously reported. However, ADT is associated with a 30% increased risk of hypertension.
CLINICAL GENITOURINARY CANCER
(2023)
Article
Oncology
Pedro C. Barata, Andrea Leith, Amanda Ribbands, Rachel Montgomery, Matthew Last, Bhakti Arondekar, Jasmina Ivanova, Alexander Niyazov
Summary: This study analyzed the real-world treatment trends for patients with metastatic castration-sensitive prostate cancer (mCSPC) between 2016 and 2020 in 5 European countries and the US. The results showed that more patients received treatment intensification with novel hormonal therapy and taxane chemotherapy in 2019-2020 compared to 2016-2018. In the US, greater use of treatment intensification with novel hormonal therapy was observed for all ethnicity groups and those with Medicare and commercial insurance status in 2019-2020. Further research is needed to understand optimal treatment sequencing in mCSPC and mCRPC.
Article
Oncology
Pedro C. Barata, Alexander Chehrazi-Raffle, Kimberly D. Allman, Aviva Asnis-Alibozek, Vijay Kasturi, Sumanta K. Pal
Summary: This article reports on the efficacy of Tivozanib in histologically diverse non-clear cell renal cell carcinoma. The study found that Tivozanib demonstrated activity and a favorable safety profile in patients with non-clear cell renal cell carcinoma, adding to the evidence supporting the use of VEGFR-TKI in this type of cancer.
Article
Oncology
Pedro C. Barata, Andrea Leith, Amanda Ribbands, Rachel Montgomery, Matthew Last, Bhakti Arondekar, Jasmina Ivanova, Alexander Niyazov
Summary: The study evaluated the impact of novel hormonal therapy (NHT) and docetaxel use in metastatic castration-sensitive prostate cancer (mCSPC) on first-line treatment patterns in metastatic castration-resistant prostate cancer (mCRPC). The results suggest that physicians consider mCSPC treatment history when making first-line treatment decisions in mCRPC.
Review
Oncology
Diana C. Simao, Kevin K. Zarrabi, Jose L. Mendes, Ricardo Luz, Jorge A. Garcia, William K. Kelly, Pedro C. Barata
Summary: Cancer treatments have changed with the introduction of immunotherapy, and new agents that redirect T-cells against cancer are rapidly emerging in multiple tumor types. However, the development of immunotherapy strategies remains a challenge in prostate cancer due to its heterogeneous and immune-suppressive tumor microenvironment.
Article
Oncology
Justine Panian, Ava Saidian, Kevin Hakimi, Archana Ajmera, William J. Anderson, Pedro Barata, Stephanie Berg, Sabina Signoretti, Steven Lee Chang, Vincent D'Andrea, Daniel George, Hannah Dzimitrowicz, Talal El Zarif, Hamid Emamekhoo, Evan Gross, Deepak Kilari, Elaine Lam, Isabel Lashgari, Sarah Psutka, Grant P. Rauterkus, Ahmed Shabaik, Bicky Thapa, Luke Wang, Nicole Weise, Kendrick Yim, Tian Zhang, Ithaar Derweesh, Rana R. McKay
Summary: This study analyzed the pathological outcomes of advanced or metastatic renal cell carcinoma patients who received immunotherapy prior to cytoreductive nephrectomy. The results showed that cytoreductive nephrectomy after immunotherapy is effective, but further prospective studies are needed to evaluate its role in the era of immunotherapy.
Article
Oncology
Diana Simao, Pedro C. Barata, Marta Alves, Ana L. Papoila, Sonia Oliveira, Peter Lawlor
Summary: This study assessed the stability of symptom clusters during disease progression and their association with survival in advanced cancer patients. Three distinct symptom clusters were identified: neuro-psycho-metabolic, gastrointestinal, and sleep impairment. The presence of the neuro-psycho-metabolic cluster and hospitalization were independently associated with worse survival.
Review
Oncology
Sree M. Lanka, Nicholas A. Zorko, Emmanuel S. Antonarakis, Pedro C. Barata
Summary: The development of immune checkpoint inhibitors (ICIs) has revolutionized the treatment landscape of several genitourinary malignancies, but the utility of immunotherapies in prostate cancer has been limited due to its immunologically cold tumor terrain. Pembrolizumab is currently the only approved ICI for metastatic castration resistant prostate cancer (mCRPC) in a select group of patients. Future research is exploring combination approaches with ICIs and other treatments to enhance their efficacy in mCRPC. Additionally, alternative checkpoint inhibitors like B7-H3 hold promise in expanding the treatment options for mCRPC.
Review
Oncology
Albert Jang, Sree M. Lanka, Hui Ting Ruan, Hamsa L. S. Kumar, Angela Y. Jia, Jorge A. Garcia, Omar Y. Mian, Pedro C. Barata
Summary: This article provides an overview of novel therapies for metastatic prostate cancer, focusing on ongoing clinical trials. The future for patients with metastatic prostate cancer is promising, with the development of new therapies such as radiopharmaceuticals. Novel agents are being designed to overcome resistance to approved therapies, and combination therapies are being tested to improve outcomes for advanced prostate cancer patients.
EXPERT REVIEW OF ANTICANCER THERAPY
(2023)
Review
Biotechnology & Applied Microbiology
Albert Jang, Jake N. Lichterman, Jeffrey Y. Zhong, Jonathan E. Shoag, Jorge A. Garcia, Tian Zhang, Pedro C. Barata
Summary: This review discusses the next generation of immune approaches for locally advanced and metastatic renal cell carcinoma (RCC), including cytokines, gut microbiota-based therapies, novel immune checkpoint agents, vaccines, and chimeric antigen receptor T cells. These approaches, evaluated as monotherapy or in combination with traditional immune checkpoint inhibitors (ICIs), hold promise for improving outcomes in RCC patients.
HUMAN VACCINES & IMMUNOTHERAPEUTICS
(2023)
Article
Endocrinology & Metabolism
Channing J. Paller, Pedro C. Barata, Justin Lorentz, Leonard J. Appleman, Andrew J. Armstrong, Tiffani A. DeMarco, Robert Dreicer, Jo Ann B. Elrod, Mark Fleming, Christopher George, Elisabeth I. Heath, Maha H. A. Hussain, Shifeng Mao, Rana R. McKay, Alicia K. Morgans, Matthew Orton, Roberto Pili, Elyn Riedel, Biren Saraiya, Joelle Sigmond, Alexandra Sokolova, Walter M. Stadler, Christina Tran, Natalie Macario, Jacob Vinson, Rebecca Green, Heather H. Cheng, PROMISE Trial Investigators
Summary: The PROMISE Registry is a novel prospective germline registry aiming to collect long-term patient outcomes data, addressing gaps in understanding resulting from recent updates in treatment approaches and genetic testing recommendations for prostate cancer. By including a broad nationwide sample, including underserved patients and those unaffiliated with major academic centers, the registry aims to provide access to germline genetic testing and collect data to understand disease characteristics and treatment responses for prostate cancer with rare germline genetic variants.