A5101569475- Prostate Cancer Treatment and Research
- Cancer Genomics and Diagnostics
- Cancer, Lipids, and Metabolism
- Radiopharmaceutical Chemistry and Applications
- Cancer Immunotherapy and Biomarkers
- Cancer Cells and Metastasis
- PARP inhibition in cancer therapy
- Lung Cancer Treatments and Mutations
- Ferroptosis and cancer prognosis
- Melanoma and MAPK Pathways
- RNA modifications and cancer
- Lipoproteins and Cardiovascular Health
- Inflammatory Biomarkers in Disease Prognosis
- Cancer Mechanisms and Therapy
- Immune Response and Inflammation
- Bone health and treatments
- Sarcoma Diagnosis and Treatment
- Genetic factors in colorectal cancer
- Cancer, Hypoxia, and Metabolism
- Immunotherapy and Immune Responses
- Medical Imaging Techniques and Applications
- Boron Compounds in Chemistry
- Estrogen and related hormone effects
- Ubiquitin and proteasome pathways
- Xenotransplantation and immune response
Epic Sciences (United States)
2021-2024
Duke University
2016-2022
Duke Medical Center
2016-2022
Duke Cancer Institute
2019-2021
Turku Centre for Biotechnology
2011
University of Turku
2011
Androgen receptor splice variant 7 (AR-V7) results in a truncated receptor, which leads to ligand-independent constitutive activation that is not inhibited by anti-androgen therapies, including abiraterone or enzalutamide. Given previous reports suggested circulating tumor cell (CTC) AR-V7 detection poor prognostic indicator for the clinical efficacy of secondary hormone we conducted prospective multicenter validation study.PROPHECY ( ClinicalTrials.gov identifier: NCT02269982) multicenter,...
Background Low-density lipoprotein receptor-related protein 1b (encoded by LRP1B ) is a putative tumor suppressor, and preliminary evidence suggests LRP1B- mutated cancers may have improved outcomes with immune checkpoint inhibitors (ICI). Methods We conducted multicenter, retrospective pan-cancer analysis of patients alterations treated ICI at Duke University, Johns Hopkins University (JHU) Michigan (UM). The primary objective was to assess the association between overall response rate...
Abstract Background Pembrolizumab is approved for patients with metastatic, microsatellite instability (MSI)‐high or mismatch repair‐deficient (dMMR) solid tumors. However, very few men prostate cancer were included in these initial studies. Methods We performed a single institution retrospective review of metastatic castrate‐resistant (mCRPC) who treated pembrolizumab. The primary objective was to describe the clinical efficacy pembrolizumab associated patient and genomic characteristics....
Abstract Purpose: Beyond enumeration, circulating tumor cells (CTCs) can provide genetic information from metastatic cancer that may facilitate a greater understanding of biology and enable precision medicine approach. Experimental Design: CTCs paired leukocytes men with castration-resistant prostate (mCRPC) were isolated blood through red cell lysis, CD45 depletion, flow sorting based on EpCAM/CD45 expression. We next performed whole genomic copy number analysis matched patient (germline)...
Abstract Purpose: While the detection of AR-V7 in circulating tumor cells (CTC) is associated with resistance to abiraterone or enzalutamide men metastatic castration-resistant prostate cancer (mCRPC), it only accounts for a minority this resistance. Neuroendocrine (NE) differentiation chromosomal instability (CIN) may be additional mechanisms that mediate Experimental Design: PROPHECY was multicenter prospective study high-risk mCRPC starting enzalutamide. A secondary objective assess Epic...
Men with circulating tumor cell (CTC) AR-V7-positive metastatic castration-resistant prostate cancer (mCRPC) have worse outcomes when treated enzalutamide/abiraterone. However, most men lack CTC AR-V7 detection, and additional predictive biomarkers are needed. We conducted a retrospective secondary analysis of the prospective PROPHECY trial (NCT02269982) mCRPC undergoing treatment enzalutamide/abiraterone, analyzing pooled germline DNA for whole-genome copy-number alterations (CNA) in 73...
Abstract Circulating tumor cell (CTC) and cell‐free (cf) DNA‐based genomic alterations are increasingly being used for clinical decision‐making in oncology. However, the concordance discordance between paired CTC cfDNA profiles remain largely unknown. We performed comparative hybridization (CGH) on CTCs cfDNA, low‐pass whole genome sequencing (lpWGS) to characterize (CNA) content two independent prospective studies of 93 men with mCRPC treated enzalutamide/abiraterone, or radium‐223....
Background: For patients with mCRPC, PSMA-targeted radioligand treatment has significantly improved the clinical outcome. A blood-based liquid biopsy assay for recognizing PSMA protein expression on circulating tumor cells may be beneficial better informing therapeutic decision-making and identifying most likely to benefit from therapy. Methods: Using high-throughput imaging digital AI pathology algorithms, a four-color immunofluorescence been developed find CTCs glass slide. Cell line...
Radium-223 is a targeted alpha-particle therapy that improves survival in men with metastatic castration resistant prostate cancer (mCRPC), particularly elevated serum levels of bone alkaline phosphatase (B-ALP). We hypothesized osteomimicry, form epithelial plasticity leading to an osteoblastic phenotype, may contribute intralesional deposition radium-223 and subsequent irradiation the tumor microenvironment.
Summary Adaptation of cancer cells to targeted therapy follows ecological paradigms observed in natural populations that encounter resource depletion and changing environments, including activation pro-survival mechanisms, migration new locations, escape predation. We identified the p38 MAPK pathway as a common molecular driver these three responses during adaptation hormone resistance prostate cancer. The is activated therapy-resistant mechanistically drives convergent through sustained AR...
5004 Background: It is unclear if CTC AR-V7 detection a valid predictive biomarker of clinical efficacy in men with mCRPC receiving A/E or just an indicator aggressive disease and high tumor burden. Methods: We conducted multicenter prospective study circulating biomarkers high-risk (PROPHECY, NCT02269982) starting A/E. The primary endpoint was association baseline radiographic/clinical progression free survival (PFS), using the Johns Hopkins modified-AdnaTest mRNA assay Epic Sciences...
e14291 Background: Low-density lipoprotein receptor-related protein 1B (LRP1B) is a putative tumor suppressor gene spanning > 500 kb on chromosome 2. A melanoma study previously reported enrichment of LRP1B mutations in responders (34%) to immune checkpoint inhibitors (ICIs) compared with non-responders (3%). Deep deletions are frequently observed non-small cell lung cancer (NSCLC, 12%), head and neck (11%), cervical (9%), bladder (8%), prostate cancers (8%). This examines the clinical...
Abstract Androgen receptor signaling inhibitors (ARSi) are a mainstay for patients with metastatic castration-resistant prostate cancer (mCRPC). However, patient response is heterogeneous and the molecular underpinnings of ARSi resistance not well elucidated. Here we performed transcriptome analysis circulating tumor cells (CTCs) peripheral blood mononuclear (PBMC) in context prospective clinical trial men mCRPC treated abiraterone (Abi) or enzalutamide (Enza). CTC RNA-sequencing identified...
160 Background: Radium-223 is a targeted alpha therapy that improves survival in men with mCRPC. The biologic basis for radium-223 efficacy not completely understood. We hypothesized PC osteomimicry, form of epithelial plasticity leading to an osteoblastic phenotype, may contribute the intralesional deposition and subsequent irradiation tumor microenvironment. Methods: conducted pharmacodynamic study bone predominant mCRPC investigate genomic phenotypic alterations circulating cells (CTCs),...
Abstract Androgen receptor signaling inhibitors (ARSi) and taxanes are mainstays for patients with metastatic castration-resistant prostate cancer (mCRPC). However, patient response is heterogeneous, the molecular underpinnings of treatment resistance not well elucidated. To identify clinically meaningful mechanisms resistance, we performed transcriptome analysis circulating tumor cells (CTCs) isolated from mCRPC enrolled in two independent prospective clinical trials: PROPHECY, a study...
147 Background: Men with CTC AR-V7 + mCRPC have very poor outcomes when treated enzalutamide/abiraterone. However, many men lack AR-V7. Here, we determined whether baseline or post-treatment DNA alterations in CTCs from negative could provide clinical utility predicting these hormonal therapies. Methods: We analyzed whole-genome copy number (CNA) using array-comparative genomic hybridization (aCGH) 48 (45 and 28 progression), whole-exome sequencing (WES) 11 abi/enza, longitudinally, focused...
Abstract There is an urgent need for more efficient and targeted methods of prostate cancer treatment. We have previously shown PLA2G7 (also known as lipoprotein-associated phospholipase A2, Lp-PLA2) to be a possible biomarker drug target especially in ERG positive cancers by combining gene expression data from tissues vivo functional RNAi studies vitro. To further study the potential management immunohistochemical staining 119 clinical samples 112 adjacent normal were performed. In...
5065 Background: CTC and ctDNA-based, actionable genomic alterations are being increasingly utilized for precision oncology therapies. However, the concordance of in DNA vs. ctDNA is not established. Methods: After CTC/ctDNA isolation, we performed whole genome copy number alteration (CNA) analysis 88 men with mCRPC treated enzalutamide (E) or abiraterone acetate (A) (n = 72), radium-223 16). We comparative hybridization (aCGH) low-pass sequencing (~0.1x, lpWGS) CNA assessment evaluated...
Abstract Background: Novel agents that inhibit the androgen receptor (AR), including abiraterone acetate and enzalutamide, have significantly prolonged life in many men with metastatic castration-resistant prostate cancer (mCRPC). However, after 1-2 years of therapy acquired resistance to these drugs is nearly universal. Therefore, identifying mechanisms innovative therapies treat enzalutamide-resistant disease represents a major unmet clinical need. Methods: In this study, we developed four...
5029 Background: Radium-223 is a targeted alpha-therapy that improves survival in men with mCRPC. The biologic basis for radium-223 efficacy not completely understood. We hypothesized PC osteomimicry, form of epithelial plasticity leading to an osteoblastic phenotype, may contribute the intralesional deposition and subsequent irradiation tumor microenvironment. Methods: conducted pharmacodynamic study (NCT02204943) bone metastatic CRPC investigate genomic phenotypic alterations circulating...
139 Background: Androgen receptor signaling inhibitors (ARSi) are a mainstay for patients with metastatic castration-resistant prostate cancer (mCRPC). However, patient response is heterogeneous and the molecular underpinnings of ARSi resistance not well elucidated. Methods: We performed transcriptome analysis circulating tumor cells (CTCs) peripheral blood mononuclear (PBMC) in context PROPHECY, prospective clinical trial men (n = 118) mCRPC treated abiraterone (Abi) or enzalutamide (Enza)....