A5000860973- Prostate Cancer Treatment and Research
- Estrogen and related hormone effects
- Radiopharmaceutical Chemistry and Applications
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Mass Spectrometry Techniques and Applications
- Cancer-related gene regulation
- RNA modifications and cancer
- Redox biology and oxidative stress
- Fibroblast Growth Factor Research
- Neuroblastoma Research and Treatments
- Receptor Mechanisms and Signaling
- Cancer-related Molecular Pathways
- Advanced biosensing and bioanalysis techniques
- Lung Cancer Treatments and Mutations
- RNA and protein synthesis mechanisms
- Mechanisms of cancer metastasis
- Advanced Breast Cancer Therapies
- Lung Cancer Research Studies
- Nutrition, Genetics, and Disease
- Immunotherapy and Immune Responses
- Colorectal Cancer Treatments and Studies
- CAR-T cell therapy research
Weill Cornell Medicine
2016-2023
Cornell University
2015-2023
Diamond Materials (United States)
2021-2023
Inserm
2010-2014
Centre de Recherche en Cancérologie de Lyon
2012-2014
Université Paris Cité
2013
Université Claude Bernard Lyon 1
2012-2013
Centre National de la Recherche Scientifique
2013
Hôpital René Huguenin
2010
Centre Léon Bérard
2010
Abstract Purpose: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of that may develop de novo or as a mechanism treatment resistance. N-myc capable driving NEPC progression. Alisertib inhibits the interaction between and its stabilizing factor Aurora-A, inhibiting signaling, suppressing tumor growth. Patients Methods: Sixty men were treated with alisertib 50 mg twice daily for 7 days every 21 days. Eligibility included metastatic at least one: small-cell neuroendocrine...
The RNA helicases DDX5 and DDX17 are members of a large family highly conserved proteins that involved in gene-expression regulation; however, their vivo targets activities biological processes such as cell differentiation, which requires reprogramming programs at multiple levels, not well characterized.Here, we uncovered mechanism by cooperate with heterogeneous nuclear ribonucleoprotein (hnRNP) H/F splicing factors to define epithelial-and myoblast-specific subprograms.We then observed...
Histologic transformation to small cell neuroendocrine prostate cancer occurs in a subset of patients with advanced as mechanism treatment resistance. Rovalpituzumab tesirine (SC16LD6.5) is an antibody-drug conjugate that targets delta-like protein 3 (DLL3) and was initially developed for lung cancer. We found DLL3 expressed most the castration-resistant (CRPC-NE) (36 47, 76.6%) adenocarcinomas (7 56, 12.5%). It shows minimal no expression localized (1 194) benign (0 103). correlates marker...
Despite recent therapeutic advances, prostate cancer remains a leading cause of cancer-related death. A subset castration-resistant cancers become androgen receptor (AR) signaling independent and develop neuroendocrine (NEPC) features through lineage plasticity. These NEPC tumors, associated with aggressive disease poor prognosis, are driven, in part, by aberrant expression N-Myc, mechanisms that remain unclear. Integrative analysis the N-Myc transcriptome, cistrome, interactome using vivo,...
Alternative promoters (AP) occur in >30% protein-coding genes and contribute to proteome diversity. However, large-scale analyses of AP regulation are lacking, little is known about their potential physiopathologic significance. To better understand the transcriptomic effect estrogens, which play a major role breast cancer, we analyzed gene by estradiol MCF7 cells using pan-genomic exon arrays. We thereby identified novel estrogen-regulated (ERG) determined AP-encoded transcripts 150...
Estrogen and androgen receptors (ER AR) play key roles in breast prostate cancers, respectively, where they regulate the transcription of large arrays genes. The activities ER AR are controlled by networks protein kinases transcriptional coregulators, including Ddx5 its highly related paralog Ddx17. Ddx17 RNA helicases also splicing regulators. Here, we report that master regulators estrogen- androgen-signaling pathways controlling both upstream downstream receptors. First, required for...
Mutations in transcription factor (TF) genes are frequently observed tumors, often leading to aberrant transcriptional activity. Unfortunately, TFs considered undruggable due the absence of targetable enzymatic To address this problem, we developed CRAFTT, a computational drug-repositioning approach for targeting TF CRAFTT combines ChIP-seq with drug-induced expression profiling identify small molecules that can specifically perturb Application ENCODE datasets revealed known drug-TF...
Abstract The molecular landscape of EGFR mutated NSCLC has evolved over time in response to changing treatment practices with inhibitors and through the expanding use NGS. With replacement first-generation reversible tyrosine kinase (TKIs) by third generation covalent TKI osimertinib as front-line therapy for patients expressing classical mutations, acquired resistance mutations have shifted near disappearance EGFR-T790M emergence growing incidence EGFR-C797S. Our understanding mutation also...
Although recent efforts have led to the development of highly effective androgen receptor (AR)-directed therapies for treatment advanced prostate cancer, a significant subset patients will progress with resistant disease including AR-negative tumors that display neuroendocrine features [neuroendocrine cancer (NEPC)]. On basis RNA sequencing (RNA-seq) data from clinical cohort tissue benign prostate, locally metastatic castration-resistant and NEPC, we developed multi-step bioinformatics...
Abstract ONC201 is the lead small molecule of imipridone class anti-cancer compounds that currently being evaluated in phase I/II advanced cancer clinical trials. a highly selective antagonist G protein-coupled receptor dopamine D2 (DRD2) has exhibited promising efficacy and an exceptional safety profile. In current study, we influence DRD2 pathway on responsiveness tumors to preclinical studies. vitro vivo studies have previously demonstrated robust glioblastoma (Allen et al 2013) lymphoma...
Abstract Background: Delta-like protein 3 (DLL3) is expressed on the surface of small cell lung cancer (SCLC) tumor-initiating cells, and DLL3 targeted antibody-drug conjugate, Rovalpituzumab tesirine (Rova-T™; SC16LD6.5), has shown promise for patients with SCLC. Neuroendocrine prostate (NEPC) an emerging late stage subtype castration resistant limited therapeutic options. Based clinical molecular similarities SCLC, we investigated expression use in NEPC xenografts. Methods: We evaluated...
Abstract Background: Targeting FGFR genetic alterations using small molecule inhibitors is a validated therapeutic strategy for urothelial carcinoma and cholangiocarcinoma. However, the current FDA-approved pan-FGFR inhibitors, erdafitinib pemigatinib, are subject to FGFR1-mediated dose-limiting toxicities (e.g., hyperphosphatemia). These treatments necessitate high rate of dose reductions, interruptions, discontinuations, thereby potentially limiting efficacy. In addition, drug-resistant...
Abstract Emerging observations from clinical trials suggest that a subset of castration resistant prostate adenocarcinomas (CRPC) eventually evolve or progress to predominantly small cell carcinoma neuroendocrine phenotype [1]. Neuroendocrine cancer (NEPC) does not typically express the androgen receptor (AR) secrete specific antigen (PSA), and often expresses markers lineage [2]. NEPC is clinically aggressive carries poor prognosis with an average survival less than one year [3, 4]....
Abstract Emerging observations from clinical trials suggest that a subset of castration resistant prostate adenocarcinomas (CRPC) eventually evolve or progress to predominantly neuroendocrine phenotype (NEPC). This transition is emerging as an important mechanism treatment resistance. cell plasticity characterized by loss androgen receptor (AR) and specific antigen (PSA), significant over-expression gene amplification MYCN (encoding N-Myc). While N-Myc bona fide driver oncogene in several...
Abstract Although neuroendocrine prostate cancer (NEPC) rarely arises de novo, up to 30% of patients with adenocarcinoma (PCa) develop NEPC features in later stages their disease as a mechanism treatment resistance hormonal therapies including abiraterone and enzalutamide. is clinically more aggressive than PCa, commonly metastases visceral organs such liver brain, can be suspected progressive disproportionately low serum PSA. There currently no effective therapy for NEPC, most survive less...