Circulating Tumor Cells Provide Information Leading to Liquid Biopsy Biomarkers
|
By LabMedica International staff writers Posted on 04 Oct 2016 |
|
Image: A micrograph of circulating tumor cells (CTCs) visualized by in situ RNA labeling (Photo courtesy of Wikimedia Commons).
Genomic analysis of pooled circulating tumor cells (CTCs) from men with metastatic castration-resistant prostate cancer revealed a reproducible, but highly complex pool of potential molecular biomarkers.
Metastatic castration-resistant prostate cancer (mCRPC) is the type of prostate cancer that does not respond to androgen deprivation or treatment with androgen receptor antagonists.
Investigators at Duke University (Durham, NC, USA) turned to CTCs as a source of genetic information with the potential to facilitate a greater understanding of tumor biology and enable a more precise approach to treatment. Towards this end, they analyzed and compared the genomes from matched CTCs and normal leukocytes obtained from 16 patients with mCRPC and primary or acquired resistance to the drug abiraterone acetate or enzalutamide.
Abiraterone acetate is a steroidal androgen synthesis inhibitor used in combination with prednisone in mCRPC. It is a prodrug to the active agent abiraterone, which has the capacity to lower circulating testosterone to an undetectable level. Enzalutamide is a synthetic non-steroidal anti-androgen used for the treatment mCRPC. This drug was reported to reduce serum prostate specific antigen (PSA) levels by 89% after a month of treatment.
CTCs and paired leukocytes were isolated from blood through red cell lysis, CD45 depletion, and flow sorting based on expression of the EpCAM/CD45 surface marker. The investigators performed whole genomic copy number analysis of CTCs and matched patient leukocytes using array-based comparative genomic hybridization (aCGH) and compiled copy gains and losses with a particular focus on those genes highly implicated in mCRPC progression and previously validated as being aberrant in metastatic tissue samples and genomic studies of reference mCRPC datasets.
Results revealed genomic gains in more than 25% of CTCs. Gains were observed in the AR, FOXA1, ABL1, MET, ERG, CDK12, BRD4, and ZFHX3 genes. Common genomic losses involved the PTEN, ZFHX3, PDE4DIP, RAF1, and GATA2 genes.
“We have developed a method that allows us to examine the whole genome of rare circulating cancer cells in the blood, which is unique in each patient, and which can change over time during treatment,” said senior author Dr. Andrew Armstrong, professor of medical oncology at Duke University. “Among the genomic changes in the patients’ individual cancers, we were able to find key similarities between the cancer cells of men who have hormone-resistant prostate cancer. Our goal is to develop a liquid biopsy that would be non-invasive, yet provide information that could guide clinical decisions.”
The study was published in the September 6, 2016, online edition of the journal Clinical Cancer Research.
Related Links:
Duke University
 Reagent.jpg)
Metastatic castration-resistant prostate cancer (mCRPC) is the type of prostate cancer that does not respond to androgen deprivation or treatment with androgen receptor antagonists.
Investigators at Duke University (Durham, NC, USA) turned to CTCs as a source of genetic information with the potential to facilitate a greater understanding of tumor biology and enable a more precise approach to treatment. Towards this end, they analyzed and compared the genomes from matched CTCs and normal leukocytes obtained from 16 patients with mCRPC and primary or acquired resistance to the drug abiraterone acetate or enzalutamide.
Abiraterone acetate is a steroidal androgen synthesis inhibitor used in combination with prednisone in mCRPC. It is a prodrug to the active agent abiraterone, which has the capacity to lower circulating testosterone to an undetectable level. Enzalutamide is a synthetic non-steroidal anti-androgen used for the treatment mCRPC. This drug was reported to reduce serum prostate specific antigen (PSA) levels by 89% after a month of treatment.
CTCs and paired leukocytes were isolated from blood through red cell lysis, CD45 depletion, and flow sorting based on expression of the EpCAM/CD45 surface marker. The investigators performed whole genomic copy number analysis of CTCs and matched patient leukocytes using array-based comparative genomic hybridization (aCGH) and compiled copy gains and losses with a particular focus on those genes highly implicated in mCRPC progression and previously validated as being aberrant in metastatic tissue samples and genomic studies of reference mCRPC datasets.
Results revealed genomic gains in more than 25% of CTCs. Gains were observed in the AR, FOXA1, ABL1, MET, ERG, CDK12, BRD4, and ZFHX3 genes. Common genomic losses involved the PTEN, ZFHX3, PDE4DIP, RAF1, and GATA2 genes.
“We have developed a method that allows us to examine the whole genome of rare circulating cancer cells in the blood, which is unique in each patient, and which can change over time during treatment,” said senior author Dr. Andrew Armstrong, professor of medical oncology at Duke University. “Among the genomic changes in the patients’ individual cancers, we were able to find key similarities between the cancer cells of men who have hormone-resistant prostate cancer. Our goal is to develop a liquid biopsy that would be non-invasive, yet provide information that could guide clinical decisions.”
The study was published in the September 6, 2016, online edition of the journal Clinical Cancer Research.
Related Links:
Duke University
Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
Complement 3 (C3) Test
GPP-100 C3 Kit
New
Gold Member
Liquid Ready-To-Use Lp(a) Reagent
Lipoprotein (a) Reagent
Latest Pathology News
- AI Integrated With Optical Imaging Technology Enables Rapid Intraoperative Diagnosis
- HPV Self-Collection Solution Improves Access to Cervical Cancer Testing
- Hyperspectral Dark-Field Microscopy Enables Rapid and Accurate Identification of Cancerous Tissues
- AI Advancements Enable Leap into 3D Pathology
- New Blood Test Device Modeled on Leeches to Help Diagnose Malaria
- Robotic Blood Drawing Device to Revolutionize Sample Collection for Diagnostic Testing
- Use of DICOM Images for Pathology Diagnostics Marks Significant Step towards Standardization
- First of Its Kind Universal Tool to Revolutionize Sample Collection for Diagnostic Tests
- AI-Powered Digital Imaging System to Revolutionize Cancer Diagnosis
- New Mycobacterium Tuberculosis Panel to Support Real-Time Surveillance and Combat Antimicrobial Resistance
- New Method Offers Sustainable Approach to Universal Metabolic Cancer Diagnosis
- Spatial Tissue Analysis Identifies Patterns Associated With Ovarian Cancer Relapse
- Unique Hand-Warming Technology Supports High-Quality Fingertip Blood Sample Collection
- Image-Based AI Shows Promise for Parasite Detection in Digitized Stool Samples
- Deep Learning Powered AI Algorithms Improve Skin Cancer Diagnostic Accuracy
- Microfluidic Device for Cancer Detection Precisely Separates Tumor Entities
Channels
Clinical Chemistry
view channel
3D Printed Point-Of-Care Mass Spectrometer Outperforms State-Of-The-Art Models
Mass spectrometry is a precise technique for identifying the chemical components of a sample and has significant potential for monitoring chronic illness health states, such as measuring hormone levels... Read more.jpg "Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)")
POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection
Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more
Highly Reliable Cell-Based Assay Enables Accurate Diagnosis of Endocrine Diseases
The conventional methods for measuring free cortisol, the body's stress hormone, from blood or saliva are quite demanding and require sample processing. The most common method, therefore, involves collecting... Read more
Molecular Diagnostics
view channel
Blood Proteins Could Warn of Cancer Seven Years before Diagnosis
Two studies have identified proteins in the blood that could potentially alert individuals to the presence of cancer more than seven years before the disease is clinically diagnosed. Researchers found... Read more (1)_1.jpg "Image: Ultrasound image of micro-histotripsy liberation of biomarkers in a tumor (Photo courtesy of Joy Wang and Pradyumna Kedarisetti)"){kind=small}
Ultrasound-Aided Blood Testing Detects Cancer Biomarkers from Cells
Ultrasound imaging serves as a noninvasive method to locate and monitor cancerous tumors effectively. However, crucial details about the cancer, such as the specific types of cells and genetic mutations... Read more_1.jpg "Image: The innovative method to customize and strengthen DNA origami structure promises breakthroughs in medicine (Photo courtesy of Shutterstock)")
.jpg "Image: The QIAstat-Dx Respiratory Panel Plus has received U.S. FDA clearance (Photo courtesy of QIAGEN)")
Hematology
view channel
Next Generation Instrument Screens for Hemoglobin Disorders in Newborns
Hemoglobinopathies, the most widespread inherited conditions globally, affect about 7% of the population as carriers, with 2.7% of newborns being born with these conditions. The spectrum of clinical manifestations... Read more
First 4-in-1 Nucleic Acid Test for Arbovirus Screening to Reduce Risk of Transfusion-Transmitted Infections
Arboviruses represent an emerging global health threat, exacerbated by climate change and increased international travel that is facilitating their spread across new regions. Chikungunya, dengue, West... Read more
POC Finger-Prick Blood Test Determines Risk of Neutropenic Sepsis in Patients Undergoing Chemotherapy
Neutropenia, a decrease in neutrophils (a type of white blood cell crucial for fighting infections), is a frequent side effect of certain cancer treatments. This condition elevates the risk of infections,... Read more
First Affordable and Rapid Test for Beta Thalassemia Demonstrates 99% Diagnostic Accuracy
Hemoglobin disorders rank as some of the most prevalent monogenic diseases globally. Among various hemoglobin disorders, beta thalassemia, a hereditary blood disorder, affects about 1.5% of the world's... Read moreImmunology
view channel.jpg "Image: The AI predictive model identifies the most potent cancer killing immune cells for use in immunotherapies (Photo courtesy of Shutterstock)")
AI Predicts Tumor-Killing Cells with High Accuracy
Cellular immunotherapy involves extracting immune cells from a patient's tumor, potentially enhancing their cancer-fighting capabilities through engineering, and then expanding and reintroducing them into the body.... Read more
Diagnostic Blood Test for Cellular Rejection after Organ Transplant Could Replace Surgical Biopsies
Transplanted organs constantly face the risk of being rejected by the recipient's immune system which differentiates self from non-self using T cells and B cells. T cells are commonly associated with acute... Read more
AI Tool Precisely Matches Cancer Drugs to Patients Using Information from Each Tumor Cell
Current strategies for matching cancer patients with specific treatments often depend on bulk sequencing of tumor DNA and RNA, which provides an average profile from all cells within a tumor sample.... Read more
Genetic Testing Combined With Personalized Drug Screening On Tumor Samples to Revolutionize Cancer Treatment
Cancer treatment typically adheres to a standard of care—established, statistically validated regimens that are effective for the majority of patients. However, the disease’s inherent variability means... Read moreMicrobiology
view channel
Integrated Solution Ushers New Era of Automated Tuberculosis Testing
Tuberculosis (TB) is responsible for 1.3 million deaths every year, positioning it as one of the top killers globally due to a single infectious agent. In 2022, around 10.6 million people were diagnosed... Read more
Automated Sepsis Test System Enables Rapid Diagnosis for Patients with Severe Bloodstream Infections
Sepsis affects up to 50 million people globally each year, with bacteraemia, formerly known as blood poisoning, being a major cause. In the United States alone, approximately two million individuals are... Read more
Enhanced Rapid Syndromic Molecular Diagnostic Solution Detects Broad Range of Infectious Diseases
GenMark Diagnostics (Carlsbad, CA, USA), a member of the Roche Group (Basel, Switzerland), has rebranded its ePlex® system as the cobas eplex system. This rebranding under the globally renowned cobas name... Read more
Clinical Decision Support Software a Game-Changer in Antimicrobial Resistance Battle
Antimicrobial resistance (AMR) is a serious global public health concern that claims millions of lives every year. It primarily results from the inappropriate and excessive use of antibiotics, which reduces... Read moreTechnology
view channel
New Diagnostic System Achieves PCR Testing Accuracy
While PCR tests are the gold standard of accuracy for virology testing, they come with limitations such as complexity, the need for skilled lab operators, and longer result times. They also require complex... Read more
DNA Biosensor Enables Early Diagnosis of Cervical Cancer
Molybdenum disulfide (MoS2), recognized for its potential to form two-dimensional nanosheets like graphene, is a material that's increasingly catching the eye of the scientific community.... Read more
Self-Heating Microfluidic Devices Can Detect Diseases in Tiny Blood or Fluid Samples
Microfluidics, which are miniature devices that control the flow of liquids and facilitate chemical reactions, play a key role in disease detection from small samples of blood or other fluids.... Read more
Breakthrough in Diagnostic Technology Could Make On-The-Spot Testing Widely Accessible
Home testing gained significant importance during the COVID-19 pandemic, yet the availability of rapid tests is limited, and most of them can only drive one liquid across the strip, leading to continued... Read moreIndustry
view channel
Danaher and Johns Hopkins University Collaborate to Improve Neurological Diagnosis
Unlike severe traumatic brain injury (TBI), mild TBI often does not show clear correlations with abnormalities detected through head computed tomography (CT) scans. Consequently, there is a pressing need... Read more
Beckman Coulter and MeMed Expand Host Immune Response Diagnostics Partnership
Beckman Coulter Diagnostics (Brea, CA, USA) and MeMed BV (Haifa, Israel) have expanded their host immune response diagnostics partnership. Beckman Coulter is now an authorized distributor of the MeMed... Read more_1.jpg "Image: Thermo Fisher will distribute Bio-Techne products across Europe (Photo courtesy of 123RF)")
