Lorne Cancer Conference 2019

Professor Matthew Ellis

Dr Matthew James Ellis a physician scientist who completed his training at the University of London (PhD) and the University of Cambridge (MB BChir). He is currently the Director for the Lester and Sue Smith Breast Center at Baylor College of Medicine where he coordinates an interdisciplinary team of oncologists, pathologists, epidemiologists, basic scientists and statisticians focused on improving our ability to prevent, detect and treat breast cancer.  In addition, he is the Associate Director for Precision Oncology at the Dan L. Duncan Comprehensive Cancer Center.  His research has focuses on estrogen receptor positive (ER+) breast cancer. He has championed neoadjuvant endocrine therapy as a non-toxic alternative to chemotherapy for promoting breast-conserving therapy in postmenopausal women with ER+ HER2- stage 2 and 3 disease (Journal of Clinical Oncology 2001).  He developed the Ki67 proliferation marker-based Preoperative Endocrine Prognostic Index (Journal of Clinical Oncology 2017) that is now undergoing a large validation study (the ALTERNATE study).  These clinical studies have provided the context and tumor specimens for seminal investigations into the ER+ breast cancer somatic genome, with insights into clonal heterogeneity (Nature Communications 2015), new tumor suppressor genes specific to ER+ disease and new therapeutic targets (Nature 2012, Nature Communications 2018).  These include activating mutations in the HER2 gene that have been shown respond to HER2 kinase inhibition in clinical trials (Cancer Discovery 2013, Clinical Cancer Research 2017).  He also is a pioneer of patient-derived xenograft research (PDX).  A PDX study in triple negative breast cancer revealed clonal remodeling during brain metastasis (Nature 2010).  PDX analysis also revealed acquired resistance to endocrine therapy is a consequence of ESR1 ligand-binding mutation; ESR1 amplification and most uniquely chromosomal translocation causing fusions between the N terminus of ESR1 and the C-terminus of genes that can confer constitutive transcriptional activity (Cell Reports 2013, 2018).  To improve our ability to understand the complex genomic changes he has been working with the Clinical Proteomic Tumor Analysis Consortium at the US National Cancer Institute to develop proteogenomic analysis of breast cancer.  This mass spectrometry-based approach recently elucidated the functional consequences of somatic mutations, narrowed candidate nominations for driver genes within large deletions and amplified regions and identified therapeutic targets (Nature 2016, Nature Communications 2017).  His work has been cited over 40,000 times (Google Scholar).  Laboratory web page https://www.bcm.edu/research/labs/matthew-ellis