Leigh Ellis
A5081026905- Prostate Cancer Treatment and Research
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Diet and metabolism studies
- Advanced Breast Cancer Therapies
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- PARP inhibition in cancer therapy
- Protein Degradation and Inhibitors
- Cancer-related Molecular Pathways
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Ferroptosis and cancer prognosis
- Cancer-related gene regulation
- Estrogen and related hormone effects
- Cancer Genomics and Diagnostics
- Cancer-related molecular mechanisms research
- Renal cell carcinoma treatment
- Antimicrobial Peptides and Activities
- Cancer therapeutics and mechanisms
- Cancer Immunotherapy and Biomarkers
- RNA modifications and cancer
- Cancer Research and Treatments
- Cutaneous lymphoproliferative disorders research
Henry M. Jackson Foundation
2023-2025
Walter Reed National Military Medical Center
2023-2025
Uniformed Services University of the Health Sciences
2023-2025
National Cancer Institute
2023-2024
Center for Cancer Research
2023-2024
Roswell Park Comprehensive Cancer Center
2010-2023
Emory University
2023
Wisconsin Institutes for Discovery
2023
University of Wisconsin–Madison
2023
Cedars-Sinai Medical Center
2021-2023
Evading cancer drugs by identity fraud Prostate growth is fueled male hormones called androgens. Drugs targeting the androgen receptor (AR) are initially efficacious, but most tumors eventually become resistant (see Perspective Kelly and Balk). Mu et al. found that prostate cells escaped effects of deprivation therapy through a change in lineage identity. Functional loss tumor suppressors TP53 RB1 promoted shift from AR-dependent luminal epithelial to AR-independent basal-like cells. In...
Evading cancer drugs by identity fraud Prostate growth is fueled male hormones called androgens. Drugs targeting the androgen receptor (AR) are initially efficacious, but most tumors eventually become resistant (see Perspective Kelly and Balk). Mu et al. found that prostate cells escaped effects of deprivation therapy through a change in lineage identity. Functional loss tumor suppressors TP53 RB1 promoted shift from AR-dependent luminal epithelial to AR-independent basal-like cells. In...
Abstract Purpose: Histone deacetylase inhibitors can alter gene expression and mediate diverse antitumor activities. Herein, we report the safety activity of histone inhibitor panobinostat (LBH589) in cutaneous T-cell lymphoma (CTCL) identify genes commonly regulated by panobinostat. Experimental Design: Panobinostat was administered orally to patients with CTCL on Monday, Wednesday, Friday each week a 28-day cycle. A dose 30 mg considered excessively toxic, subsequent were treated at...
A hallmark of prostate cancer progression is dysregulation lipid metabolism via overexpression fatty acid synthase (FASN), a key enzyme in de novo synthesis. Metastatic castration-resistant (mCRPC) develops resistance to inhibitors androgen receptor (AR) signaling through variety mechanisms, including the emergence constitutively active AR variant V7 (AR-V7). Here, we developed an FASN inhibitor (IPI-9119) and demonstrated that selective inhibition antagonizes CRPC growth metabolic...
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...
Abstract Systemic metabolic alterations associated with increased consumption of saturated fat and obesity are linked risk prostate cancer progression mortality, but the molecular underpinnings this association poorly understood. Here, we demonstrate in a murine model, that high-fat diet (HFD) enhances MYC transcriptional program through favour histone H4K20 hypomethylation at promoter regions regulated genes, leading to cellular proliferation tumour burden. Saturated intake (SFI) is also an...
Abstract Lineage plasticity, the ability of a cell to alter its identity, is an increasingly common mechanism adaptive resistance targeted therapy in cancer. An archetypal example development neuroendocrine prostate cancer (NEPC) after treatment adenocarcinoma (PRAD) with inhibitors androgen signaling. NEPC aggressive variant that aberrantly expresses genes characteristic (NE) tissues and no longer depends on androgens. Here, we investigate epigenomic basis this by profiling histone...
Abstract Sarcomatoid and rhabdoid (S/R) renal cell carcinoma (RCC) are highly aggressive tumors with limited molecular clinical characterization. Emerging evidence suggests immune checkpoint inhibitors (ICI) particularly effective for these tumors, although the biological basis this property is largely unknown. Here, we evaluate multiple trial real-world cohorts of S/R RCC to characterize their features, outcomes, immunologic characteristics. We find that harbor distinctive features may...
Abstract Neuroendocrine carcinomas (NEC) are tumors expressing markers of neuronal differentiation that can arise at different anatomic sites but have strong histological and clinical similarities. Here we report the chromatin landscapes a range human NECs show convergence to activation common epigenetic program. With particular focus on treatment emergent neuroendocrine prostate cancer (NEPC), analyze cell lines, patient-derived xenograft (PDX) models samples existence two distinct NEPC...
Abstract c-MYC (MYC) is a major driver of prostate cancer tumorigenesis and progression. Although MYC overexpressed in both early metastatic disease associated with poor survival, its impact on transcriptional reprogramming remains elusive. We demonstrate that overexpression significantly diminishes the androgen receptor (AR) program (the set genes directly targeted by AR protein) luminal cells without altering expression. Analyses clinical specimens reveal concurrent low high programs...
Histone deacetylase inhibitors (HDACi) can elicit a range of biological responses that affect tumor growth and survival, including inhibition cell cycle progression, induction cell-selective apoptosis, suppression angiogenesis, modulation immune responses, show promising activity against hematological malignancies in clinical trials. Using the Emu-myc model B lymphoma, we screened tumors with defined genetic alterations apoptotic pathways for therapeutic responsiveness to HDACi vorinostat....
Immunosuppressive factors such as regulatory T cells (Tregs) limit the efficacy of immunotherapies. Histone deacetylase (HDAC) inhibitors have been reported to antitumor activity in different malignancies and immunomodulatory effects. Herein, we report Tregs-targeting immune-promoting effect a class I specific HDAC inhibitor, entinostat, combination with either IL-2 murine renal cell carcinoma (RENCA) model or survivin-based vaccine therapy (SurVaxM) castration resistant prostate cancer (CR...
Tyrosine kinase inhibitors (TKI) targeting angiogenesis via inhibition of the vascular endothelial growth factor pathway have changed medical management metastatic renal cell carcinoma. Although treatment with TKIs has shown clinical benefit, these drugs will eventually fail patients. The potential mechanisms resistance to are poorly understood. To address this question, we obtained an excisional biopsy a skin metastasis from patient clear carcinoma who initially had response sunitinib and...
Abstract Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive cancer, defined by the progression localized disease to metastasis, is responsible for majority of cancer–associated mortality. Recent gene expression profiling has proven successful in predicting outcome cancer patients; however, they have yet provide targeted therapy approaches that could inhibit a patient's metastatic disease. Experimental Design: We interrogated total seven...
Mediator kinases CDK19 and CDK8, pleiotropic regulators of transcriptional reprogramming, are differentially regulated by androgen signaling but both upregulated in castration-resistant prostate cancer (CRPC). Genetic or pharmacological inhibition CDK8 reverses the phenotype restores sensitivity CRPC xenografts to deprivation vivo. Prolonged CDK8/19 inhibitor treatment combined with castration not only suppresses growth also induces tumor regression cures. Transcriptomic analysis revealed...
The gut microbiota modulates response to hormonal treatments in prostate cancer (PCa) patients, but whether it influences PCa progression remains unknown. Here, we show a reduction fecal alpha-diversity correlating with increase tumour burden two distinct groups of hormonotherapy naïve patients and three murine models. Fecal transplantation (FMT) from high volume is sufficient stimulate the growth mouse revealing existence microbiome-cancer crosstalk. Analysis microbial-related pathways mice...
Abstract Cancer cells exhibit metabolic plasticity to meet oncogene-driven dependencies while coping with nutrient availability. A better understanding of how systemic metabolism impacts the accumulation metabolites that reprogram tumor microenvironment (TME) and drive cancer could facilitate development precision nutrition approaches. Using Hi-MYC prostate mouse model, we demonstrated an obesogenic high-fat diet (HFD) rich in saturated fats accelerates c-MYC–driven invasive through...
Circular RNA (circRNA) is a class of noncoding with regulatory potentials. Its role in the transdifferentiation prostate and lung adenocarcinoma into neuroendocrine cancer (NEPC) small cell (SCLC) remains unexplored. Here, we identified circRMST as an exceptionally abundant circRNA predominantly expressed NEPC SCLC, strong conservation between humans mice. Functional studies using shRNA, siRNA, CRISPR-Cas13, Cas9 consistently demonstrate that essential for tumor growth expression ASCL1,...
A major barrier for cancer immunotherapy is the presence of suppressive cell populations in patients with cancer, such as myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM), which contribute to immunosuppressive microenvironment that promotes tumor growth metastasis. Tasquinimod a novel antitumor agent currently at an advanced stage clinical development treatment castration-resistant prostate cancer. target tasquinimod inflammatory protein S100A9, has been...