Yuzhuo Wang

Yuzhuo Wang
University of British Columbia - Vancouver | UBC · Department of Urologic Sciences

Ph.D. FCAHS

About

389
Publications
105,705
Reads
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15,076
Citations
Additional affiliations
July 2014 - present
BC Cancer Research Centre
Position
  • Researcher
July 2014 - present
University of British Columbia - Vancouver
Position
  • Professor (Full)
July 2009 - June 2014
University of British Columbia - Vancouver
Position
  • Professor (Associate)

Publications

Publications (389)
Article
Full-text available
Current chemotherapeutic regimens have only modest benefit for non-small cell lung cancer (NSCLC) patients. Cumulative toxicities/drug resistance limit chemotherapy given after the first-line regimen. For personalized chemotherapy, clinically relevant NSCLC models are needed for quickly predicting the most effective regimens for therapy with curati...
Article
Full-text available
The common preference of cancers for lactic acid-generating metabolic energy pathways has led to proposals that their reprogrammed metabolism confers growth advantages such as decreased susceptibility to hypoxic stress. Recent observations, however, suggest that it generates a novel way for cancer survival. There is increasing evidence that cancers...
Article
Full-text available
Standardized and reproducible pre-clinical models that recapitulate the dynamics of prostate cancer (PCa) are urgently needed. We established a bank of transplantable patient-derived PCa xenografts that capture the biological and molecular heterogeneity currently confounding prognostication and therapy development. Xenografts preserved the histopat...
Article
Full-text available
Cancer stem cells (CSCs) have been implicated as the seeds of treatment resistance and metastasis, which are the most deadly features of a neoplasm. However, an unequivocal definition of the CSC phenotype is still missing. A common feature of normal and aberrant stem cells is their ability to enter a prolonged dormant state. Cancer dormancy is a ke...
Article
Full-text available
Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer. NEPC arises de novo only rarely; the disease predominantly develops from adenocarcinoma in response to drug-induced androgen receptor signalling inhibition, although the mechanisms behind this transdifferentiation are a subject of debate. The survival of patients with NEP...
Article
Full-text available
The androgen receptor (AR) signaling inhibitor enzalutamide (enza) is one of the principal treatments for metastatic castration-resistant prostate cancer (CRPC). Several emergent enza clinical resistance mechanisms have been described, including lineage plasticity in which the tumors manifest reduced dependency on the AR. To improve our understandi...
Article
Full-text available
Lineage plasticity of prostate cancer is associated with resistance to androgen receptor (AR) pathway inhibition (ARPI) and supported by a reactive tumor microenvironment. Here we show that changes in chondroitin sulfate (CS), a major glycosaminoglycan component of the tumor cell glycocalyx and extracellular matrix, is AR-regulated and promotes the...
Raw Data
Nanocarriers have received special attention in biomedicine for the treatment of various diseases, especially cancer, as one of the leading causes of death worldwide. Nanocarriers can improve the potential of contemporary strategies in cancer therapy and also provide new methods for diagnosis and biosensing. The present review focuses on the biomed...
Article
Full-text available
Background: One of the most malignant tumors in men is prostate cancer that is still incurable due to its heterogenous and progressive natures. Genetic and epigenetic changes play significant roles in its development. The RNA molecules with more than 200 nucleotides in length are known as lncRNAs and these epigenetic factors do not encode protein....
Article
Full-text available
Urological cancers are among the most common malignancies around the world. In particular, bladder cancer severely threatens human health due to its aggressive and heterogenous nature. Various therapeutic modalities have been considered for the treatment of bladder cancer although its prognosis remains unfavorable. It is perceived that treatment of...
Article
In mammalian cells, DNA is wrapped around histone octamers (collectively referred to as nucleosomes) which form a physical barrier to all DNA-based processes. The switch/sucrose non-fermentable (SWI/SNF) is a multi-subunit chromatin remodeling complex that uses energy from ATP hydrolysis to reposition or eject nucleosomes at non-coding regulatory e...
Article
The switch/sucrose non-fermentable (SWI/SNF) complex plays a crucial role in chromatin remodeling and is recurrently altered in over 20% of human cancers. Here, we developed a proteolysis targeting chimera (PROTAC) degrader of ATPase subunits of the SWI/SNF complex, SMARCA2 and SMARCA4. Intriguingly, we found androgen receptor (AR)/forkhead box A1...
Article
Androgen deprivation therapy (ADT) and androgen receptor pathway inhibition (ARPI) remains the standard of care for advanced prostate cancer (PCa). As part of its canonical activities, the androgen receptor (AR) plays an important role in PCa metabolism. AR inhibition with ARPI subjects PCa cells to acute metabolic stress caused by reduced biosynth...
Article
Numerous cancers, including prostate cancer (PCa), have been shown to be addicted to transcription programs driven by specific genomic sites known as superenhancers (SEs). Recently, it has been proposed that the robust transcription of genes at such SEs is enabled by the formation of phase-separated condensates by transcription factors and coactiva...
Article
Long noncoding RNAs (lncRNAs) are RNA molecules involved in gene regulation at transcriptional, post-transcriptional, and epigenetic levels. lncRNAs participate in regulating apoptosis and autophagy in pancreatic cancer (PCa) and can promote and/or decrease the proliferation rate of tumor cells. The metastasis of PCa cells is tightly regulated by l...
Article
Full-text available
Androgen deprivation therapy (ADT) is the standard therapy for men with advanced prostate cancer (PCa). PCa often responds to ADT and enters a dormancy period, which can be recognized clinically as a minimal residual disease. However, the majority of these patients will eventually experience a relapse in the form of castration-resistant PCa with po...
Article
Introduction: The application of doxorubicin (DOX) in cancer therapy has been limited due to its drug resistance and poor internalization. Graphene oxide (GO) nanostructures have the capacity for DOX delivery while promoting its cytotoxicity in cancer. Areas covered: The favorable characteristics of GO nanocomposites, preparation method, and app...
Article
Full-text available
Prostate cancer is a leading cause of death worldwide and new estimates revealed prostate cancer as the leading cause of death in men in 2021. Therefore, new strategies are pertinent in the treatment of this malignant disease. Macroautophagy/autophagy is a “self-degradation” mechanism capable of facilitating the turnover of long-lived and toxic mac...
Article
Full-text available
Non-coding RNAs (ncRNAs) are a large family of RNA molecules with no capability in encoding proteins. However, they participate in developmental and biological processes and their abnormal expression affects cancer progression. These RNA molecules can function as upstream mediators of different signaling pathways and enhancer of zeste homolog 2 (EZ...
Article
Full-text available
Treatment-induced tumor dormancy is a state in cancer progression where residual disease is present but remains asymptomatic. Dormant cancer cells are treatment-resistant and responsible for cancer recurrence and metastasis. Prostate cancer treated with androgen-deprivation therapy (ADT) often enters a dormant state. ADT-induced prostate cancer dor...
Article
Full-text available
Significance Glutamate-ureido-lysine (GUL) probes are specific for prostate-specific membrane antigen (PSMA), overexpressed by most prostate cancers. This antigen can be lost as the cancer progresses. Recent reports have indicated that GUL probes can still identify these PSMA-negative tumors, indicating that the expression of alternative PSMA-like...
Article
Full-text available
The switch/sucrose non-fermentable (SWI/SNF) complex has a crucial role in chromatin remodelling ¹ and is altered in over 20% of cancers 2,3 . Here we developed a proteolysis-targeting chimera (PROTAC) degrader of the SWI/SNF ATPase subunits, SMARCA2 and SMARCA4, called AU-15330. Androgen receptor (AR) ⁺ forkhead box A1 (FOXA1) ⁺ prostate cancer ce...
Article
Full-text available
Neuroendocrine (NE) prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer (PCa) arising either de novo or from transdifferentiated prostate adenocarcinoma following androgen deprivation therapy (ADT). Extensive computational analysis has identified a high degree of association between the long noncoding RNA (lncRNA) H19...
Article
Full-text available
In recent years, patient-derived xenografts (PDXs) have attracted much attention as clinically relevant models for basic and translational cancer research. PDXs retain the principal histopathological and molecular heterogeneity of their donor tumors and remain stable across passages. These characteristics allow PDXs to offer a reliable platform for...
Article
Full-text available
Long noncoding RNAs (lncRNAs) have a wide range of functions in health and disease, but many remain uncharacterized because of their complex expression patterns and structures. The genetic loci encoding lncRNAs can be subject to accelerated evolutionary changes within the human lineage. HAR1 is a region that has a significantly altered sequence com...
Article
Full-text available
Geminin and its binding partner Cdt1 are essential for the regulation of DNA replication. Here we show that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP binds Geminin at endogenous level and regulates DNA replication. SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127. This poly-ubiquitina...
Article
Full-text available
Mutations in SPOP E3 ligase gene are reportedly associated with genome-wide DNA hypermethylation in prostate cancer (PCa) although the underlying mechanisms remain elusive. Here, we demonstrate that SPOP binds and promotes polyubiquitination and degradation of histone methyltransferase and DNMT interactor GLP. SPOP mutation induces stabilization of...
Article
Full-text available
Background Androgen deprivation therapy (ADT) remains the leading systemic therapy for locally advanced and metastatic prostate cancers (PCa). While a majority of PCa patients initially respond to ADT, the durability of response is variable and most patients will eventually develop incurable castration-resistant prostate cancer (CRPC). Our research...
Article
Full-text available
The prevalence of neuroendocrine prostate cancer (NEPC) arising from adenocarcinoma (AC) upon potent androgen receptor pathway inhibition is increasing. Deeper understanding of NEPC biology and development of novel therapeutic agents are needed. However, research is hindered by the paucity of research models, especially cell lines developed from NE...
Article
Full-text available
Metastatic neuroendocrine prostate cancer (NEPC) is a highly aggressive disease, whose incidence is rising. Long non‐coding RNAs (lncRNAs) represent a large family of disease‐ and tissue‐specific transcripts, most of which are still functionally uncharacterized. Thus, we set out to identify the highly‐conserved lncRNAs that play a central role in N...
Preprint
Full-text available
Numerous cancers, including prostate cancer (PCa), are addicted to transcription programs driven by superenhancers (SEs). The transcription of genes at SEs is enabled by the formation of phase-separated condensates by transcription factors and co-activators with intrinsically disordered regions. The androgen receptor (AR), main oncogenic driver in...
Article
Chemotherapy is the main treatment used for cancer patients failing surgery. Doxorubicin (DOX) is a well-known chemotherapeutic agent capable of suppressing proliferation in cancer cells and triggering apoptosis via inhibiting topoisomerase II activity and producing DNA breaks. This activity of DOX restrains mitosis and cell cycle progression. Howe...
Article
Full-text available
Treatment-induced adaptive pathways converge to support androgen receptor (AR) reactivation and emergence of castration-resistant prostate cancer (PCa) after AR pathway inhibition (ARPI). We set out to explore poorly defined acute adaptive responses that orchestrate shifts in energy metabolism after ARPI and identified rapid changes in succinate de...
Article
Full-text available
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 a set of androgen receptor (AR) binding sites with increased AR binding intensity (ARBS-gained). While ARB...
Article
Full-text available
Immune evasion and altered metabolism, where glucose utilization is diverted to increased lactic acid production, are two fundamental hallmarks of cancer. Although lactic acid has long been considered a waste product of this alteration, it is now well accepted that increased lactic acid production and the resultant acidification of the tumor microe...
Poster
Long non-coding RNAs (lncRNAs) have been characterized as key players in several cancer-associated processes such as tumorigenesis and drug resistance. Emerging evidence indicates that lncRNAs affect initiation and progression of several cancers, including prostate cancer (PCa) and its advanced forms, such as metastatic castration resistant prostat...
Article
Full-text available
Prostate cancer (PCa) progression is driven by androgen receptor (AR) signaling. Unfortunately, androgen-deprivation therapy and the use of even more potent AR pathway inhibitors (ARPIs) cannot bring about a cure. ARPI resistance (i.e. castration-resistant PCa, CRPC) will inevitably develop. Previously, we demonstrated that GRB10 is an AR transcrip...
Preprint
p>Prostate-specific membrane antigen (PSMA) is highly overexpressed in most prostate cancers and is clinically visualized using PSMA-specific probes incorporating Glutamate-Ureido-Lysine (GUL). PSMA is effectively absent from certain high-mortality, treatment-resistant subsets of prostate cancers, such as neuroendocrine prostate cancer (NEPC); howe...
Chapter
Emerging evidence indicates that long non-coding RNAs (lncRNAs) regulate key cellular phenotypes, including proliferation, survival, and epithelial-to-mesenchymal transition (EMT). Specific lncRNAs have been described as oncogenic and oncosuppressive in a variety of solid and haematological malignancies. The expression of some of these transcripts...
Article
Full-text available
Immunotherapies are revolutionizing the clinical management of a wide range of cancers. However, intrinsic or acquired unresponsiveness to immunotherapies does occur due to the dynamic cancer immunoediting which ultimately leads to immune escape. The evolutionarily conserved histone modifier enhancer of zeste 2 (EZH2) is aberrantly overexpressed in...
Article
Full-text available
Background: Castration-resistant prostate cancer (CRPC) is an incurable malignancy. Long noncoding RNAs (lncRNAs) play key roles in drug resistance. Materials & methods: LncRNA HORAS5 role in cabazitaxel resistance (i.e., cell-count, IC 50 and caspase activity) was studied via lentiviral-mediated overexpression and siRNA-based knockdown. Genes expr...
Article
Full-text available
Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial proliferation that is most commonly encountered as an incidental finding in the peritoneal cavity. There is controversy in the literature about whether WDPM is a neoplasm or a reactive process and, if neoplastic, whether it is a variant or precursor of epithelial malignant...
Article
Full-text available
Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer. It develops mainly via NE transdifferentiation of prostate adenocarcinoma in response to androgen receptor (AR)-inhibition therapy. The study of NEPC development has been hampered by a lack of clinically relevant models. We previously established a unique and first-in-fie...
Article
Full-text available
Neuroendocrine prostate cancer (NEPC) is the most virulent form of prostate cancer. Importantly, our recent work examining metastatic biopsy samples demonstrates NEPC is increasing in frequency. In contrast to prostate adenocarcinomas that express a luminal gene expression program, NEPC tumors express a neuronal gene expression program. Despite thi...
Article
Background Activating mutations in AKT1 and PIK3CA are undercharacterised in metastatic castration-resistant prostate cancer (mCRPC), but are linked to activation of phosphatidylinositol 3-kinase (PI3K) signalling and sensitivity to pathway inhibitors in other cancers. Objective To determine the prevalence, genomic context, and clinical associatio...
Article
Prostate cancer (PCa) is the third most common malignancy worldwide. Novel and effective therapeutic targets are needed for PCa. The purpose of this study was to discover novel therapeutic targets for PCa by performing advanced analysis on PCa RNA sequencing (RNAseq) data from The Cancer Genome Atlas (TCGA). Weighted correlation-network analysis (W...
Article
Full-text available
Background: Current in vitro modeling systems do not fully reflect the biologic and clinical diversity of prostate cancer (PCa). Organoids are 3D in vitro cell cultures that recapitulate disease heterogeneity, retain prostate gland architecture, and mirror parental tumor characteristics. Methods: To make better use of organoid models in the PCa...
Article
Full-text available
The Open University's first one-day symposium on treatment-emergent neuroendocrine prostate cancer attracted world-leading figures, early career researchers and industry colleagues. The symposium proved insightful into the ‘real-world’ impact and current problems faced in the diagnosis and treatment of neuroendocrine prostate cancer. It was importa...
Article
Purpose: Although the incidence of de novo neuroendocrine prostate cancer (NEPC) is rare, recent data suggests that low expression of prostate-specific membrane antigen (PSMA) is associated with a spectrum of neuroendocrine (NE) hallmarks and androgen receptor (AR)-suppression in prostate cancer (PC). Previous clinical reports indicate that PCs wit...
Article
Full-text available
Outcomes for metastatic Ewing sarcoma and osteosarcoma are dismal and have not changed for decades. Oxidative stress attenuates melanoma metastasis, and melanoma cells must reduce oxidative stress to metastasize. We explored this in sarcomas by screening for oxidative stress sensitizers, which identified the class I HDAC inhibitor MS-275 as enhanci...
Article
Full-text available
Background Long non-coding RNAs (lncRNAs) have been recently identified as key players in several cancer-associated pathways such as metastasis and drug resistance. Emerging evidence indicates that the HORAS5 lncRNA (i.e. linc00161) modulates drug response in different malignancies. In a recently published study, we have shown that HORAS5 promotes...
Article
Full-text available
CULLIN3-based E3 ubiquitin ligase substrate-binding adaptor gene SPOP is frequently mutated in prostate cancer (PCa). PCa harboring SPOP hotspot mutants (e.g., F133V) are resistant to BET inhibitors because of aberrant elevation of BET proteins. Here, we identified a previously unrecognized mutation Q165P at the edge of SPOP MATH domain in primary...
Article
An increasingly recognized mechanism of prostate cancer resistance is the transdifferentiation from adenocarcinoma to treatment-emergent neuroendocrine prostate cancer (t-NEPC), an extremely aggressive malignancy. The incidence of t-NEPC has been increasing in recent years, in part due to novel treatments that target the androgen receptor pathway....
Article
Full-text available
Context: It is increasingly evident that non-protein-coding regions of the genome can give rise to transcripts that form functional layers of the cancer genome. One of most abundant classes in these regions is long noncoding RNAs (lncRNAs). They have gained increasing attention in prostate cancer (PCa) and paved the way for a greater understanding...
Article
Background: Androgen deprivation therapy (ADT) is the treatment of choice for metastatic prostate cancer (PCa). After an initial response to ADT, PCa cells can generate castration resistant (CRPC) or neuroendocrine (NEPC) malignancies, which are incurable. T-type calcium channels (TTCCs) are emerging as promising therapeutic targets for several ca...
Conference Paper
Treatment-emergent neuroendocrine prostate cancer (t-NEPC) is a lethal subtype of advanced prostate cancer that occurs via NE transdifferentiation of prostate adenocarcinomas in response to androgen receptor (AR)-inhibition therapy. Study of t-NEPC has been hampered by a lack of clinically relevant models. We previously established a unique and fir...
Preprint
Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial proliferation that is most commonly encountered as an incidental finding in the peritoneal cavity. There is controversy in the literature about whether WDPM is a neoplasm or a reactive process, and if neoplastic, whether it is a variant or precursor of epithelial malignant...
Data
Fig. S3. Expression of Long and short HORAS5 splice variants in PCa cell lines and LTL PDXs.
Data
Fig. S6. HORAS5 silencing does not alter cell migration potential.
Data
Fig. S10. Several key oncogenic proteins are down‐regulated upon HORAS5 knockdown.<