Matthew J. C. Ellis, M.B., B.Chir., Ph.D.
- Professor
- Department of Medicine
- Oncology Division
- Breast Oncology Section
- Oncology Division
- Department of Medicine
- Research interests
- Insulin-like growth factor signaling and breast cancer
- Endocrine therapy for breast cancer
- Signal transduction therapy for breast cancer
- Preoperative systemic therapy for breast cancer
- Array based analysis of breast cancer gene expression
- Breast cancer clinical trial correlative science
Research
The demonstration that the HER2 gene is amplified in breast cancer heralded the “genomic era” which ultimately led to major clinical advances for HER2-positive disease. The HER2 discovery was based on a search for cancer specific anomalies in the cellular homologs of the acutely transforming retroviral oncogenes described in birds and mammals. However HER2 gene amplification is now recognized to be only one of a large number of somatic mutations that occur in breast cancer, most of which have been identified through genomic screening techniques. Large scale tumor DNA resequencing projects, focused on a small number of tumors and the analysis of many genes, suggest that by the time breast cancer enters the terminal phase approaching ten or eleven individual somatic mutations may have accumulated. Similarly, array comparative hybridization experiments have uncovered multiple gene amplification and deletion events. The complexity of these changes has given rise to the concept of a “cancer genome atlas” in which all the recurring mutations in cancer are documented in publicly available data bases to assist clinical investigation and translational medicine. Understanding the clinical and biological significance of these somatic changes must represent one of the most important challenges facing breast cancer researchers today because when complete, a functionally annotated breast cancer genome atlas will provide predictive/prognostic biomarkers and therapeutic opportunities that will transform our approach to this common disease.
In the last ten years my clinical and laboratory efforts have therefore focused on the development of a luminal (hormone receptor positive) breast cancer genome atlas. In the early years our focus was on developing and promoting clinical collaborations, clinical trials and establishment of high quality (snap frozen) tumor specimen banks that are essential for genomic research. During these efforts we established a body of work on the practice of treating postmenopausal women with large palpable hormone receptor rich tumors with four months of an aromatase inhibitor before surgery. This treatment has now become a standard of care when a low toxicity approach is indicated for promoting breast conservation in older patients. This benefit to patients has driven our subsequent clinical trial success. Most recently our grant application collaborations have extended to include the American College of Surgeons Oncology Group with the activation of the national neoadjuvant endocrine therapy trial Z1031 that I lead as principal investigator. We have also established links with several UK centers with tissue banks from similar types of studies. The ultimate goal of these intensely collaborative efforts is to create specimen banks and biomarker data from thousands of patients to create sufficient statistical power to robustly link genomic screens to clinical outcomes so we can eventually focus our basic science efforts on lethal genetic events that offer the best new opportunities for therapeutic intervention.
From the scientific perspective our neoadjuvant trials allow a determination of the estrogen dependence of individual tumors and since the therapy is mechanistically simple - estrogen withdrawal though aromatase inhibition - biomarker research should be inherently more likely to produce a robust response predictor than efforts to predict, for example, the effectiveness of multi-agent chemotherapy. Our medium-term scientific goal is therefore to compare individual tumor genomic profiles with information on primary tumor aromatase inhibitor responsiveness to determine the constellation of genetic events that underlie estrogen-independent growth/endocrine therapy resistance. Over the last year, as a result of multiple nested grants from the NIH in the form of an R01, an Avon Foundation/NCI partner in progress award and Komen support from two CRAFT awards we have been able to complete a phase 2 trial of 115 patients who received four months of the aromatase inhibitor letrozole. We are in the process of completing a comprehensive analysis of the tumor samples accrued, including "whole genome" gene expression chips, high resolution array comparative hybridization analysis and candidate gene sequencing. In addition we have also begun to apply these techniques to samples from the Z1031 trial where the final sample size is 375 patients. Finally we have recently developed collaboration with the NHGRI and the Washington University Genome Center for large scale candidate gene sequencing of tumor DNA samples from both the R01 funded trial and Z1031. These long term efforts are finally reaching fruition and an initial publication on the complex amplicon structure of luminal breast cancer and the impact of individual gene amplification events on response to neoadjuvant aromatase inhibition and long-term outcomes is planned for mid 2010.
Our eventual goal is to deliverer new clinical grade diagnostic tests based on our genomic discoveries. To focus on this problem we developed a U01 to fund collaborations between Washington University, the University of Utah, and the University of North Carolina, Chapel Hill. This funded project focuses on developing a qPCR based biological classification of breast cancer. A patent by the three universities has been filed on our initial findings and licensing negotiations are proceeding. The gene lists we are currently generating, particularly those from the marriage of expression profiling and array comparative hybridization, also suggest a host of new therapeutic targets are ready to be exploited. Functional characterization of these genes has begun and will be a major new focus in my laboratory for the next five years.
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Cross-talk between signal transduction pathways and ER signaling in endocrine resistant breast cancer, with opportunities for targeted intervention.
From: Ellis M, Ma C
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Biographical Sketch
Education
| 1978-1980 | 2nd M.B., King’s College, University of London, UK |
| 1980-1981 | B.Sc. (hons), St. Mary's Hospital Medical School, University of London, UK |
| 1981-1984 | M.B., B.Chir., Queens’ College & School of Clinical Medicine, University of Cambridge, UK |
| 1986 | MRCP, Royal College of Physicians, London, Regents Park London, UK |
| 1988-1991 | Ph.D., Royal Postgraduate Medical School, University of London, UK |
Professional Training
| 1984-1985 | House Officer, Addenbrookes, Papworth Hinchingbrook Hospitals, Cambridge Medical School, UK |
| 1985 | Senior House Officer, General Medicine & Gastroenterology, Hammersmith Hospital, London, UK |
| 1985-1986 | Senior House Officer, Radiotherapy & Oncology, Pulmonary Medicine, Churchill Hospital, Oxford, UK |
| 1986-1988 | Registrar, General & Pulmonary Medicine, Gastroenterology, Hammersmith Medical Registrar Rotations, London, UK |
| 1988-1991 | Research Fellow, Gene Expression Laboratory, Imperial Cancer Research Fund, London, UK |
| 1991-1992 | MRC Travelling Research Fellow, Lombardi Comprehensive Cancer Center, Washington, DC |
| 1992-1994 | Medical Oncology Fellow, Georgetown University Hospital, Washington, DC |
Academic Positions
| 1994-1996 | Instructor, Department of Medicine, Georgetown University, Washington, DC |
| 1996-2000 | Assistant Professor, Department of Medicine, Georgetown University, Washington, DC |
| 2000-2003 | Associate Professor, Department of Medicine, Duke University, Durham, NC |
| 2003-2008 | Associate Professor, Department of Medicine, Washington University, St. Louis, MO |
| 2003-2011 | Head, Section of Medical Oncology, Division of Oncology, Department of Medicine, Washington University, St. Louis, MO |
| 2003-present | Co-Director, Clinical and Translational Research, Siteman Comprehensive Cancer Center, St. Louis, MO |
| 2003-present | Anheuser Busch Professor of Medical Oncology, Washington University, St. Louis, MO |
| 2003-present | Director, Breast Health Program, Washington University and Barnes-Jewish Hospital, St. Louis, MO |
| 2007-present | McDonnell International Scholars Academy, Washington University, St. Louis, MO University Ambassador to Brazil and the University of Campinas, SP |
| 2008-present | Professor, Department of Medicine, Washington University, St. Louis, MO |
| 2011-present | Director, Section of Breast Oncology, Division of Oncology, Department of Medicine, Washington University, St. Louis, MO |
Board Certification
| 2004 | Internal Medicine |
| 2005 | Medical Oncology |
Professional Recognition
| 2003-present | Vice Chair, CALGB Breast Committee |
| 2006-present | Chair, ACOSOG Medical Oncology Committee |
| 2009-present | Vice Chair, ACOSOG Breast Cancer Committee |
| 2006-2007 | Best Doctors in St. Louis, http://www.cejkasearch.com |
| 2007 | Outstanding Clinical Trial Accrual, ACOSOG |
| 2008-2010 | Best Doctors in America, http://www.bestdoctors.com |
| 2009 | Standing Member, Clinical Oncology Study Section, NCI |
| 2010 | Co-Chair, AACR Annual Meeting Committee |
| 2010 | Co-Chair, Breast Cancer Genome Atlas, NCI |
| 2011 | Co-Chair, CPTAC Steering committee |
Awards
| 2001 | Elected Fellow, Royal College of Physicians |
Government Consultant Appointments
| Endocrinologic and Metabolic Drugs Advisory Committee #69 | |
| 1998 | Food and Drug Administration, Expert Advisor |
| 2002 | Program for the Assessment of Cancer Clinical Tests (PACCT) Breast Cancer Working Group Member, National Institutes of Heath |
| 2006 | Chair, Fresh Frozen Working Group for the BIG/NCI Cooperative Groups |
| 2007 | Avon-NCI PFP Blue Ribbon Panel, Advisory Board Member |
| 2007 | Special Review Panel for NSABP Trial Protocol P4 |
| 2007, 2009 | Presentation to the National Cancer Advisory Board |
| 2008, 2009 | CTEP Clinical Trial Concept Review |
| 2007, 2008, 2009, 2010 | CTEP/TBCI Concept Review |
Editorial Boards
| 2000-2006 | Breast Cancer, a Year Book Quarterly |
| 2003-2005 | Journal of Clinical Oncology |
| 2002-2006 | Endocrine Related Cancer |
| 2004-present | Breast Cancer Research and Treatment |
| 2005-present | Biomed Central (BMC) Cancer |
| 2011-present | Cancer Discovery |
National Organizations
| 1997-2001 | Member, Breast Cancer Working Group of the Solid Tumor Correlative Science Committee, Cancer and Lymphoma Group B (CALGB) |
| 2001-2005 | Chairman, Breast Cancer Working Group of the Solid Tumor Correlative Science Committee, Cancer and Lymphoma Group B (CALGB) |
| 2001-present | Cadre Member, Breast Cancer Committee, Cancer and Lymphoma Group B (CALGB) |
| 2004-present | Member, Breast Cancer Committee, American College of Surgeons Oncology Group |
| 2005-present | Vice Chair, Breast Cancer Committee, Cancer and Lymphoma Group B (CALGB) |
| 2007-present | Chairman, Medical Oncology Committee, American College of Surgeons Oncology Group |
| 2009-present | Vice Chair, Breast Committee, American College of Surgeons Oncology Group |
| 2010-present | External Co-chair of the Breast Disease Working Group for “The Cancer Genome Atlas” |
National Meeting Organization
| 1999 | American Association for Cancer Research, Program Committee Subcommittee member for “Cell Growth Signaling Pathways: Cell Biology Aspects” |
| 1999 | Chairperson for Minisymposium “Protein kinases in tumor progression/regression”, AACR Annual Meeting |
| 2004, 2005, 2006, 2010 | Member of Program Committee, ASCO |
| 2011 | Co-chair, Program Committee AACR Annual Meeting |
Grant Review
| 1996, 1999, 2001 | Study Section, Department of Veterans Affairs |
| 2002, 2003, 2008 | Review Panel, NCI/AVON/SPORE Partners in Progress Award Program |
| 2003 | Primary Grant Reviewer, UK Breast Cancer Campaign |
| 2003-2007 | CALGB Fellowship and Junior Faculty Awards |
| 2005, 2006 | NCI Breast Cancer SPORE Study Section |
| 2005, 2006, 2007, 2008 | Clinical Trial Reviewer for Cancer Research UK |
| 2005, 2006, 2008 | Breakthrough Cancer UK Grant Review |
| 2006 | Cancer Research UK, Fellowship Awards |
| 2007 | NCI Cancer Center Review, P30 Cancer Center Support Grant Application from the Kimmel Cancer Center at Thomas Jefferson University |
| 2008 | NCI Grant Review: Special Emphasis Panel: Cancer Genetics and Profiling |
| 2008 | Susan G. Komen Race for the Cure Pathobiology Study Section |
| 2009-present | Standing Member, Clinical Oncology Study Section, NCI |
| 2010 | MRC Quinquennial Review |
Non-government Advisory Boards
| 2003-present | External Advisory Board, UCSF SPORE in Breast Cancer |
| 2007-present | Scientific Advisory Board, Avon Foundation |
| 2007, 2008 | External Reviewer for Developmental Projects, MD Anderson SPORE in Breast Cancer |
| 2010 | Scientific Advisory Board, NSABP |
| 2010 | Scientific Advisory Board, Samsung Cancer Center |
- Updated: February 9, 2012
