Article
Cell Biology
Shimiao Zhu, Zhao Yang, Zheng Zhang, Hongli Zhang, Songyang Li, Tao Wu, Xuanrong Chen, Jianing Guo, Aixiang Wang, Hao Tian, Jianpeng Yu, Changwen Zhang, Lei Su, Zhiqun Shang, Changyi Quan, Yuanjie Niu
Summary: Resistance to antiandrogen is lethal for castration-resistant prostate cancer (CRPC). In this study, we identified HOXB3 as an independent risk factor for progression and death in metastatic CRPC. We demonstrated that HOXB3 activation was associated with WNT pathway genes expression, and suppression of HOXB3 sensitized CRPC to abiraterone treatment. Our findings suggest that targeting HOXB3 may benefit a subgroup of CRPC resistant to antiandrogen therapy.
CELL DEATH & DISEASE
(2023)
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)
Article
Biochemistry & Molecular Biology
Daniel Bakopoulos, Sofya Golenkina, Callum Dark, Elizabeth L. Christie, Besaiz J. Sanchez-Sanchez, Brian M. Stramer, Louise Y. Cheng
Summary: This study shows that insulin and TGF-beta signalling converge via a BMP antagonist sog to regulate ECM remodelling in adipose tissue. In tumour bearing animals, Sog also modulates TGF-beta signalling to regulate ECM accumulation. Activation of insulin signalling, inhibition of TGF-beta signalling, or modulation of ECM levels can rescue tissue wasting in the presence of tumor.
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
Multidisciplinary Sciences
Fanying Tang, Duo Xu, Shangqian Wang, Chen Khuan Wong, Alexander Martinez-Fundichely, Cindy J. Lee, Sandra Cohen, Jane Park, Corinne E. Hill, Kenneth Eng, Rohan Bareja, Teng Han, Eric Minwei Liu, Ann Palladino, Wei Di, Dong Gao, Wassim Abida, Shaham Beg, Loredana Puca, Maximiliano Meneses, Elisa de Stanchina, Michael F. Berger, Anuradha Gopalan, Lukas E. Dow, Juan Miguel Mosquera, Himisha Beltran, Cora N. Sternberg, Ping Chi, Howard Scher, Andrea Sboner, Yu Chen, Ekta Khurana
Summary: This study classified CRPC into different subtypes using ATAC-seq, RNA-seq, and DNA sequencing. The identified subtypes include AR-dependent, neuroendocrine, Wnt-dependent, and stem cell-like subtypes driven by AP-1 transcription factors. Transcriptomic signatures were used for patient classification, and SCL was found to be the second most common subtype of CRPC.
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.
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
Oncology
Masaki Shiota, Yohei Sekino, Shigehiro Tsukahara, Tatsuro Abe, Fumio Kinoshita, Kenjiro Imada, Shohei Ueda, Miho Ushijima, Shohei Nagakawa, Takashi Matsumoto, Eiji Kashiwagi, Ario Takeuchi, Junichi Inokuchi, Takeshi Uchiumi, Yoshinao Oda, Masatoshi Eto
Summary: The study indicates that Y-box binding protein-1 (YB-1) is overexpressed in castration-resistant prostate cancer (CRPC) through gene amplification, which contributes to the progression of CRPC by regulating the expression of AR and AR V7. Additionally, YB-1 amplification is associated with poor prognosis in CRPC.
Article
Oncology
Sandy Srinivas
Summary: Significant advancements in the management of mCRPC include the development of newer imaging methods utilizing PSMA PET and radionuclide ligands, as well as the use of PARP inhibitors and Cabazitaxel in treatment. Investigators are focusing on sequencing therapies based on previous exposure to optimize treatment choices for mCRPC patients.
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
(2021)