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Matthew J. Ellis, MB, BChir, PhD
Director of the Lester and Sue Smith Breast Center
Professor of Medicine and
Cellular and Molecular Biology
Baylor College of Medicine
- Seeking new methods to detect when treatments aren’t working, so that patients can get the right drug at the right time.
- Development of a blood-based assay to measure tumor DNA to determine how well a cancer therapy is working.
- These efforts will lead to better, more personalized treatment and improve breast cancer outcomes.
Changes in tumor DNA occur throughout the course of tumor development. It is now possible to measure these in the blood of patients during the course of therapy through a new technology called liquid biopsy. Though still experimental, liquid biopsy offers a promising alternative to imaging a tumor after a course of therapy. By collecting blood during treatment intervals, scientists can monitor changes in tumor DNA as they happen and respond in real time when a treatment is not working. Dr. Ellis is testing a liquid biopsy assay in patients undergoing treatment for breast cancer to see if it can accurately predict results by imaging.
Full Research Summary
Tumors develop because of the accumulation of changes in the genome called "somatic mutations", which occur during the course of tumor development. They are only present in the tumor cells, not in normal cells. Remarkably, somatic mutations can be now detected in the blood using new and very sensitive technologies called circulating tumor DNA (ctDNA) assays.
Dr. Ellis and colleagues are collecting blood samples from patients enrolled in an adjuvant chemotherapy trial and are analyzing tumor DNA from patients’ blood. They will develop a ctDNA assay to track the effectiveness of the treatment in eradicating the disseminated cells. If successful, the low-cost, sensitive, and specific assay could become a powerful clinical tool in personalized medicine by assessing treatment effectiveness early in the course of therapy so that changes in therapy can be considered while the cancer is still curable.
This pilot study aims to predict the results of the patient’s next CT/PET scan and is expected to reduce the number of ineffective cycles of treatment that a patient will receive. This type of test may reduce toxicity and cost and encourage patients to try experimental treatment if the effectiveness can be more rapidly determined.
Dr. Ellis is also the lead investigator on a study to develop and test experimental models of metastatic breast cancer called patient-derived xenografts (PDX). This project, which is part of the Evelyn H. Lauder Founder's Fund effort, brings together a team of investigators with strong track records of investigating breast cancer biology and therapeutics using models generated directly from patients with breast cancer.
Separately, Dr. Ellis is collaborating with Dr. Cynthia Ma on a Phase III neoadjuvant treatment trial to validate a test called modified Preoperative Endocrine Prognostic Index (PEPI) in predicting endocrine therapy sensitivity and to develop a mutation-based classification of ER+ breast cancer that will inform new approaches to reduce the recurrence rate.
Originally from the United Kingdom, Matthew Ellis completed his medical training in the U.K. at the Universities of Cambridge and London. After 11 years at Washington University in St Louis, Dr. Ellis is the incoming Director of the Lester and Sue Smith Breast Center and Professor of Medicine and Cellular and Molecular Biology at Baylor College of Medicine, Houston Texas. His research interests include the identification of genes that affect responses and resistance to endocrine therapy in breast cancer Patients. Dr. Ellis is also co-principal investigator for the NCI-funded Proteome Characterization Center and co-project leader for The Cancer Genome Atlas (TCGA) Breast Project. Dr. Ellis was the recipient of ASCO's 2015 Gianni Bonadonna Breast Cancer Award and Lecture for his pioneering research into the clinical relevance of activating mutations in HER2 and in the deployment of patient-derived xenografts for the pharmacological annotation of breast cancer genomes.