A5100325679- Prostate Cancer Treatment and Research
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Radiopharmaceutical Chemistry and Applications
- Estrogen and related hormone effects
- Cancer-related gene regulation
- Advanced Proteomics Techniques and Applications
- Prostate Cancer Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Cancer-related Molecular Pathways
- Cancer Research and Treatments
- Receptor Mechanisms and Signaling
- Cell death mechanisms and regulation
- Immunotherapy and Immune Responses
- Wnt/β-catenin signaling in development and cancer
- Lung Cancer Treatments and Mutations
- Protein Degradation and Inhibitors
- Cancer, Stress, Anesthesia, and Immune Response
- Hepatitis C virus research
BC Cancer Agency
2015-2025
Binzhou University
2025
Binzhou Medical University
2025
Beijing Hospital
2012-2024
University of British Columbia
2015-2024
Shanghai First People's Hospital
2024
Institute of Electrical and Electronics Engineers
2024
Tulane University
2019-2023
Chinese Academy of Medical Sciences & Peking Union Medical College
2005-2023
Institute of Hematology & Blood Diseases Hospital
2005-2023
Abstract Mechanisms controlling the emergence of lethal neuroendocrine prostate cancer (NEPC), especially those that are consequences treatment-induced suppression androgen receptor (AR), remain elusive. Using a unique model AR pathway inhibitor–resistant cancer, we identified AR-dependent control neural transcription factor BRN2 (encoded by POU3F2) as major driver NEPC and aggressive tumor growth, both in vitro vivo. Mechanistic studies showed directly suppresses transcription, which is...
Standardized and reproducible preclinical models that recapitulate the dynamics of prostate cancer are urgently needed. We established a bank transplantable patient-derived xenografts capture biologic molecular heterogeneity currently confounding prognostication therapy development. Xenografts preserved histopathology, genome architecture, global gene expression donor tumors. Moreover, their aggressiveness matched patient observations, response to androgen withdrawal correlated with tumor...
More potent targeting of the androgen receptor (AR) in advanced prostate cancer is driving an increased incidence neuroendocrine (NEPC), aggressive and treatment-resistant AR-negative variant. Its molecular pathogenesis remains poorly understood but appears to require TP53 RB1 aberration. We modeled development NEPC from conventional prostatic adenocarcinoma using a patient-derived xenograft found that placental gene PEG10 de-repressed during adaptive response AR interference subsequently...
// Francesco Crea 1 , Akira Watahiki 1,2 Luca Quagliata 3 Hui Xue Larissa Pikor 4 Abhijit Parolia 1,5 Yuwei Wang Dong Lin Wan L. Lam William Farrar 6 Takao Isogai 7 Rudolf Morant 8 Serenella Castori-Eppenberger Kim N. Chi 2,9 Yuzhuo and Cheryl D. Helgason Experimental Therapeutics, BC Cancer Agency Research Centre, Vancouver BC, Canada. 2 The prostate General Hospital, Molecular Pathology Unit, Institute of Pathology, University Hospital Basel, Switzerland Genetics Integrative Oncology, 5...
Neuroendocrine prostate cancer (NEPC), a lethal form of the disease, is characterized by loss androgen receptor (AR) signaling during neuroendocrine transdifferentiation, which results in resistance to AR-targeted therapy. Clinically, genomically and epigenetically, NEPC resembles other types poorly differentiated tumors (NETs). Through pan-NET analyses, we identified ONECUT2 as candidate master transcriptional regulator NETs. ectopic expression adenocarcinoma synergizes with hypoxia...
Malignant peritoneal mesothelioma (PeM) is a rare and fatal cancer that originates from the lining of abdomen. Standard treatment PeM limited to cytoreductive surgery and/or chemotherapy, no effective targeted therapies for exist. Some immune checkpoint inhibitor studies have found positivity be associated with worse prognosis. To search novel therapeutic targets PeM, we performed comprehensive integrative multi-omics analysis genome, transcriptome, proteome 19 treatment-naïve in particular,...
Neuroendocrine prostate cancer (NEPC) is a highly aggressive subtype of (PCa) for which the median survival remains less than year. Current treatments are only palliative in nature, and lack suitable pre-clinical models has hampered previous efforts to develop novel therapeutic strategies. Addressing this need, we have recently established first vivo model complete neuroendocrine transdifferentiation using patient-derived xenografts. Few genetic differences were observed between parental PCa...
The glucocorticoid and androgen receptors (GR AR) can commonly regulate up to 50% of their target genes in prostate cancer (PCa) cells. GR expression is stimulated by castration therapy, which has been proposed be one mechanism that compensates for AR signaling blockade promotes castration-resistant PCa (CRPC) progression. However, whether functions as a driver CRPC or marker reflecting activity remains unclear. Here, we applied tissue microarrays show protein levels were elevated but...
The management of castration-resistant prostate cancer (CRPC) is a major challenge in the clinic. Androgen receptor signaling-directed strategies are not curative CRPC therapy, and new targeting alternative, key properties needed. Using reprogrammed glucose metabolism (aerobic glycolysis), cells typically secrete excessive amounts lactic acid into their microenvironment, promoting development, survival, progression. Cellular secretion thought to be predominantly mediated by MCT4, plasma...
Resistance to next-generation anti-androgen enzalutamide (ENZ) constitutes a major challenge for the treatment of castration-resistant prostate cancer (CRPC). By performing genome-wide ChIP-seq profiling in ENZ-resistant CRPC cells we identify set androgen receptor (AR) binding sites with increased AR intensity (ARBS-gained). While ARBS-gained loci lack canonical response elements (ARE) and pioneer factor FOXA1 motifs, they are highly enriched CpG islands unmethylated dinucleotide-binding...
Abstract Prostate cancer (PCa) is mainly managed with androgen deprivation therapy (ADT), but this often leads to a dormant state and subsequent relapse as lethal castration-resistant prostate (CRPC). Using our unique PCa patient-derived xenograft (PDX) dormancy models, we investigated critical phase discovered selective increase in B7-H4 expression during the period following mouse host castration. This finding supported by observations clinical specimens of patients treated ADT....
Background While it has been challenging to establish prostate cancer patient‐derived xenografts (PDXs), with a take rate of 10‐40% and long latency time, multiple groups throughout the world have developed methods for successful establishment serially transplantable human PDXs using variety immune deficient mice. In 2014, Movember Foundation launched Global Action Plan 1 (GAP1) project support an international collaborative PDX program involving eleven groups. Between these consortium...
Long non-coding RNAs (lncRNAs) can orchestrate oncogenic or tumor-suppressive functions in cancer biology. Accordingly, PCGEM1 and PRNCR1 were implicated progression of prostate (PCa) as transcriptional co-regulators the androgen receptor (AR). However, these findings recently refuted asserting that neither gene physically binds to AR. Despite evidence for differing AR programs vivo vitro, studies investigating AR-regulation genes hitherto have only been conducted vitro. Here, we further...
Genomic analyses of hundreds prostate tumors have defined a diverse landscape mutations and genome rearrangements, but the transcriptomic effect this complexity is less well understood, particularly at individual tumor level. We selected cohort 25 high-risk tumors, representing lethal phenotype, applied deep RNA-sequencing matched whole sequencing, followed by detailed molecular characterization. Ten were exposed to neo-adjuvant hormone therapy expressed marked evidence response in all...
Article26 September 2019Open Access Source DataTransparent process The novel BET-CBP/p300 dual inhibitor NEO2734 is active in SPOP mutant and wild-type prostate cancer Yuqian Yan Department of Biochemistry Molecular Biology, Mayo Clinic College Medicine Science, Rochester, MN, USA Search for more papers by this author Jian Ma Urology, Fudan University Shanghai Cancer Center, Shanghai, China Oncology, Medical College, University, Dejie Wang Dong Lin Experimental Therapeutics, BC Research...