A5015713542- Prostate Cancer Treatment and Research
- PARP inhibition in cancer therapy
- Computational Drug Discovery Methods
- Cancer therapeutics and mechanisms
- Epigenetics and DNA Methylation
- Molecular Biology Techniques and Applications
- DNA Repair Mechanisms
- Ubiquitin and proteasome pathways
- Cancer Genomics and Diagnostics
- Radiopharmaceutical Chemistry and Applications
- Estrogen and related hormone effects
- Genomics and Chromatin Dynamics
- Cancer Cells and Metastasis
- Cancer, Lipids, and Metabolism
- Protein Degradation and Inhibitors
- Heat shock proteins research
- Cancer-related Molecular Pathways
- Histone Deacetylase Inhibitors Research
- Chemical Reactions and Isotopes
- Cardiac electrophysiology and arrhythmias
- Radiation Therapy and Dosimetry
- Steroid Chemistry and Biochemistry
- Hippo pathway signaling and YAP/TAZ
- Peptidase Inhibition and Analysis
- Radiation Effects in Electronics
National Cancer Institute
2017-2024
Center for Cancer Research
2017-2024
Cancer Institute (WIA)
2019
National Institutes of Health
2017-2018
ORCID
2018
University of Illinois Chicago
2010-2015
University of Illinois Urbana-Champaign
2010
<h3>Background</h3> Checkpoint inhibitors have not been effective for prostate cancer as single agents. Durvalumab is a human IgG1-K monoclonal antibody that targets programmed death ligand 1 and approved by the U.S. Food Drug Administration locally advanced or metastatic urothelial advanced, unresectable stage 3 non-small cell lung cancer. Olaparib, poly (ADP-ribose) polymerase inhibitor, has demonstrated an improvement in median progression-free survival (PFS) select patients with...
Abstract Purpose: Prostate cancer translational research has been hampered by the lack of comprehensive and tractable models that represent genomic landscape clinical disease. Metastatic castrate-resistant prostate (mCRPC) patient-derived xenografts (PDXs) recapitulate genetic phenotypic diversity We sought to establish a representative, preclinical platform PDX-derived organoids is experimentally facile for high-throughput mechanistic analysis. Experimental Design: Using 20 from LuCaP mCRPC...
Aberrations in epigenetic processes, such as histone methylation, can cause cancer. Retinoblastoma binding protein 2 (RBP2; also called JARID1A or KDM5A) demethylate tri- and dimethylated lysine 4 H3, which are marks for transcriptionally active chromatin, whereas the multiple endocrine neoplasia type 1 (MEN1) tumor suppressor promotes H3K4 methylation. Previous studies suggested that inhibition of RBP2 contributed to suppression by retinoblastoma (pRB). Here, we show genetic ablation Rbp2...
The retinoblastoma tumor suppressor protein pRb restricts cell growth through inhibition of cycle progression. Increasing evidence suggests that also promotes differentiation, but the mechanisms are poorly understood, and key question remains as to how differentiation in cells can be enhanced order diminish their aggressive potential. Previously, we identified histone demethylase KDM5A (lysine [K]-specific 5A), which demethylates H3 on Lys4 (H3K4), a pRB-interacting counteracting pRB's role...
Androgen-receptor (AR) inhibitors, including enzalutamide, are used for treatment of all metastatic castration-resistant prostate cancers (mCRPCs). However, some patients develop resistance or never respond. We find that the transcription factor CREB5 confers enzalutamide in an open reading frame (ORF) expression screen and tumor xenografts. overexpression is essential enzalutamide-resistant patient-derived organoid. In AR-expressing cancer cells, interactions enhance AR activity at a subset...
Epigenetic regulation underlies the robust changes in gene expression that occur during development. How precisely epigenetic enzymes contribute to development and differentiation processes is largely unclear. Here we show one of removes activating mark trimethylated lysine 4 on histone H3, (K)-specific demethylase 5A (KDM5A), reinforces effects retinoblastoma (RB) family transcriptional repressors differentiation. Global location analysis showed KDM5A cooccupies a substantial portion target...
Irinotecan and topotecan are used to treat a variety of different cancers. However, they have limitations, including chemical instability severe side effects. To overcome these we developed the clinical indenoisoquinolines: LMP400 (indotecan), LMP776 (indimitecan), LMP744. The purpose study is build molecular rationale for phase II trials.
The PI3K-AKT pathway has pleiotropic effects and its inhibition long been of interest in the management prostate cancer, where a compensatory increase PI3K signaling reported following androgen receptor (AR) blockade. Prostate cancer cells can also bypass AR blockade through induction other hormone receptors, particular glucocorticoid (GR). Here we demonstrate that AKT significantly decreases cell proliferation both cytostatic cytotoxic effects. effect is enhanced by most pronounced models...
// Hong Pan 1, 2, 3 , Keith H. Jansson Michael L. Beshiri JuanJuan Yin Lei Fang Supreet Agarwal Holly Nguyen 4 Eva Corey Ying Zhang 1 Jie Liu HuiTing Fan HongSheng Lin and Kathleen Kelly Laboratory of Cancer, Guang'anmen Hospital, China Academy Chinese Medicine Sciences, Beijing, 2 Clinical Medical College, Beijing University Medicine, Genitourinary Cancer Pathogenesis, Center for Research, National Institute, Institutes Health, Bethesda, Maryland, USA Department Urology, Washington,...
Abstract The development of new treatments for castrate resistant prostate cancer (CRPC) must address such challenges as intrinsic tumor heterogeneity and phenotypic plasticity. Combined PTEN/ TP53 alterations represent a major genotype CRPC (25–30%) are associated with poor outcomes. Using tumor-derived, castration-resistant Pten/Tp53 null luminal cells comprehensive, high-throughput, mechanism-based screening, we identified several vulnerabilities among >1900 compounds, including...
Antibody-drug conjugates(ADCs) are promising targeted cancer therapy; however, patient selection based solely on target antigen expression without consideration for cytotoxic payload vulnerabilities has plateaued clinical benefits. Biomarkers to capture patients who might benefit from specific ADCs have not been systematically determined any cancer. We present a comprehensive therapeutic and biomarker analysis of B7H3-ADC with pyrrolobenzodiazepine(PBD) in 26 treatment-resistant, metastatic...
Abstract To resist lineage-dependent therapies such as androgen receptor inhibition, prostate luminal epithelial adenocarcinoma cells often adopt a stem-like state resulting in lineage plasticity and phenotypic heterogeneity. Castrate-resistant can transition to neuroendocrine (NE) occasionally amphicrine, co-expressed NE, phenotypes. We developed castrate-resistant cancer (CRPC) patient-derived organoid models that preserve heterogeneity of the originating tumor, including an amphicrine...
Recruitment of transcriptional and epigenetic factors to their targets is a key step in regulation. Prominently featured recruitment are the protein domains that bind specific histone modifications. One such domain plant homeodomain (PHD), found several chromatin-binding proteins. The factor RBP2 has multiple PHD domains, however, they have different functions (Figure 4). In particular, C-terminal domain, oncogenic fusion human leukemia, binds trimethylated lysine 4 H3 (H3K4me3). transcript...
Recruitment of transcriptional and epigenetic factors to their targets is a key step in regulation. Prominently featured recruitment are the protein domains that bind specific histone modifications. One such domain plant homeodomain (PHD), found several chromatin-binding proteins. The factor RBP2 has multiple PHD domains, however, they have different functions (Figure 4). In particular, C-terminal domain, oncogenic fusion human leukemia, binds trimethylated lysine 4 H3 (H3K4me3)1. transcript...
ABSTRACT Purpose To resist lineage-dependent therapies such as androgen receptor inhibition in prostate cancer, cancer cells often adopt a stem-like state resulting lineage-plasticity and phenotypic heterogeneity. We assessed the dynamics of lineage determination cellular subpopulation expansion treatment-resistant adenocarcinoma, amphicrine, small cell neuroendocrine castrate resistant cancers (CRPCs). Experimental Design developed CRPC patient-derived organoid models that preserve...
ABSTRACT The PI3K-AKT pathway has pleiotropic effects, and its inhibition long been of interest in the management prostate cancer, where a compensatory increase PI3K signaling reported following Androgen Receptor (AR) blockade. Prostate cancer cells can also bypass AR blockade through induction other hormone receptors, particular glucocorticoid receptor (GR). Here we demonstrate that AKT significantly decreases cell proliferation both cytostatic cytotoxic effects. effect is enhanced by most...
Abstract Antibody-drug conjugates (ADCs) are promising targeted cancer therapy; however, patient selection based solely on target antigen expression without consideration for cytotoxic payload vulnerabilities has plateaued clinical benefits. Biomarkers to capture patients who might benefit from specific ADCs have not been systematically determined any cancer. We present a comprehensive therapeutic and biomarker analysis of B7H3-ADC with pyrrolobenzodiazepine(PBD) in 26 treatment-resistant,...
<p>Tables of compounds, recombinant proteins, antibodies, and primers used</p>
<p>Supplementary Figures</p>