Expression Profiling of Circulating Tumor Cells
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Non-technical overview of the research topic and relevance to breast cancer: The spread of cancer to distant sites, known as metastasis, is responsible for virtually all breast cancer related deaths. Detection of circulating tumor cells (CTCs) has been demonstrated to be prognostic in both metastatic and non-metastatic breast cancer. Our study uses a highly innovative method to isolate pure CTCs, allowing for detailed molecular descriptions of these rare cells. Our research group has recently discovered a method for the isolation and characterization of CTCs in breast cancer. These rare cancer cells in the blood (CTCs) appear to be precursors of metastatic disease. We wish to identify and target them before they have advanced to the point that they may be found through imaging or physical examination. Cancers are highly variable - although sophisticated technology exists to classify primary tumors, primary tumor biology does not reveal the entire story as to why some patients recur and others do not. This is likely because measurable indications of disease, known as biomarkers, of the non-aggressive disease within a bulk tumor dilute important markers for aggressive disease.
 
 
 
 
 
 
 
 The question(s) or central hypotheses of the research: We hypothesize that molecular profiling (identifying molecular patterns or signatures) of CTCs may be a clinically useful biomarker to predict response to neoadjuvant chemotherapy in Stage II-III breast cancer. Neoadjuvant chemotherapy (NC) is defined as chemotherapy given prior to surgery. 
 
 
 
 
 
 
 
 The general methodology: Our CTC isolation strategy involves separating rare cancer cells from millions of red and white cells found in blood. We propose to study whether sequencing the molecular patterns of CTCs from non-metastatic breast cancer patients may provide clinically relevant information that could potentially help guide patient treatment. Sequencing involves collecting all the available genetic information that describes which genes are turned on or off in cells. We propose to conduct a prospective study enrolling 120 Stage II-III newly diagnosed breast cancer patients to screen for CTCs. Our innovative method allows us to separate pure cancer cells from peripheral blood, asking patients to undergo a minimally invasive blood draw of 2 small tubes (20 milliliters) of blood. Our primary objective is to determine if CTC profiling can predict for complete tumor eradication after neoadjuvant chemotherapy. This is determined by comparing CTC signatures to pathology results at the time of definitive cancer surgery. We will also look for evidence of stem cell markers or markers indicating that CTCs may or may not be actively dividing cells. We will use two independent technologies to verify our CTC signature results are correct. 
 
 
 
 
 
 
 
 Innovative elements of the project: To our knowledge, this is the first such method permitting successful capture of CTCs suitable for profiling pure CTCs across many thousands of genes (the whole genome) without bias from contaminating white cells. We will carry out a series of studies in order to better understand the relationship of CTCs to their primary tumors and understand whether CTCs may be used as a surrogate for metastasis. Our study uses a highly innovative method to isolate pure CTCs, allowing for detailed molecular characterization of these rare cells. Such profiling allows us to learn which genes are active in CTCs. We will test several important hypotheses to gain a better understanding of the biology of CTCs. This proposal will have a potential impact on the eradication of breast cancer by determining if CTC gene profiling may play a useful clinical role in predicting for response to NC. This type of approach has tremendous potential for personalized medicine, allowing for a variety of molecular approaches never before possible. My laboratory seeks to move the field beyond counting circulating tumor cells to a more detailed molecular understanding of how circulating tumor cells fit into the process of metastasis and how to target these cells before clinically detectable metastases occur. If successful, detailed molecular profiling of patients’ CTCs may potentially benefit all stages of breast cancer patients as an opportunity to assess in real time the current state of a patient’s tumor biology and explore rational therapeutic strategies and novel targets for treatment.