OMIC AND MULTIDIMENSIONAL SPATIAL ATLAS OF METASTATIC BREAST CANCERS

Overview

Omic and Multidimensional Spatial (OMS) Atlas

The overall goal of the HTAN OMS Atlas Center is to elucidate mechanisms by which metastatic breast cancers become resistant to current generation pathway- and immune checkpoint-targeted treatments. The OMS Atlas is motivated by the appreciation that these treatments are often effective in primary tumors but only transiently effective in the metastatic setting. Possible resistance mechanisms include tumor-intrinsic genomic instability and epigenomic plasticity, as well as events extrinsic to the cancer cells, including chemical and mechanical signals from the microenvironments, production of mechanical extracellular matrix barriers and/or changes in vasculature that reduce drug and/or immune cell access, nanoscale cancer cell-microenvironment interactions that reduce drug efficacy, and a plethora of immune resistance mechanisms, such as loss of HLA expression and antigen presentation, and immune exhaustion. These mechanisms likely vary between patients and within individual patients and change with time as tumors respond to therapeutic attack. The OMS Atlas will focus on elucidating resistance mechanisms in two specific current generation clinical trial scenarios: (a) hormone receptor-positive breast cancer (HRBC) undergoing treatment with a CDK4/6 inhibitor in combination with endocrine therapy and (b) triple negative breast cancer (TNBC) undergoing treatment with a PARP inhibitor and an immunomodulatory agent.

Principal Investigators

JOE GRAY, Ph.D.

Dr. Joe W. Gray, a physicist and engineer by training, is the Director of the Center for Spatial Systems Biomedicine and Associate Director for Biophysical Oncology at the Knight Cancer Institute, both at Oregon Health & Science University. Dr. Gray’s research program uses integrated omic analysis and multiscale imaging to identify drug resistance mechanisms that are intrinsic to the tumor or that derive from tumor-microenvironment interactions. He has contributed to development of a number of important analytical tools including high-speed chromosome sorting, BrdUrd/DNA analysis of cell proliferation, Fluorescence In Situ Hybridization, Comparative Genomic Hybridization and End Sequence Profiling. Currently, he is applying omic and multiscale image analysis approaches to identify mechanisms of therapeutic resistance and vulnerability in metastatic breast cancer. He is author of more 500 publications and holds 80 US patents.

GORDON B. MILLS, M.D., Ph.D.

Dr. Gordon B. Mills earned his M.D. and Ph.D. in biochemistry and completed his training in Obstetrics and Gynecology at the University of Alberta. Prior to moving to the Knight Cancer Institute, Dr. Mills was at the MD Anderson Cancer Center, the number one ranked cancer center in the United States. At the Knight Cancer Institute at the Oregon Health & Science University, Dr. Mills is Director of Precision Oncology and SMMART trials. He is responsible for the implementation of an integrated program of tumor analysis, decision-making, and implementation of novel precision oncology trials. Dr. Mills is recognized as one of the most highly quoted scientists in the world with over 1,000 publications, and he also holds more than 20 patents.

GEORGE V. THOMAS, M.D.

Dr. George V. Thomas is Professor of Pathology at Oregon Health & Science University. He is a member of the Knight Cancer Institute, Director of the Histopathology Shared Resource, and Associate Medical Director of the Knight Diagnostic Laboratories. Dr. Thomas completed his pathology residency and fellowships in the Harvard and UCLA medical systems and was on the faculty at UCLA prior to joining OHSU. As a specialist in genitourinary cancers, he has served as an invited member of the Mouse Models of Human Cancer Consortium, Stand Up 2 Cancer Prostate Dream Team, Mechanisms of Cancer Therapeutics study section, TGCA Papillary Kidney Cancer Analysis Working Group, and the TCGA Pan-Cancer Metabolism Working Group. Clinically, he has leveraged his molecular insights to lead the molecular diagnostics efforts that guide the precision oncology program at the Knight Cancer Institute.

JEREMY GOECKS, Ph.D.

Dr. Jeremy Goecks is an Associate Professor of Biomedical Engineering and Computational Biology at Oregon Health & Science University (OHSU). His research program develops computational tools and infrastructure for analysis of large biomedical datasets. At the OHSU Knight Cancer Institute, Dr. Goecks leads the development of computational methods for precision oncology that integrate clinical, imaging, and omics data to (1) predict tumor response to targeted therapies and (2) identify tumor cellular pathways associated with adaptation and susceptibility to therapies. He has leadership positions in several national and international computational biomedical infrastructure projects funded by NCI, NHGRI, and NSF. He also is a lead investigator for the Galaxy Project (http://galaxyproject.org), a web-based computational workbench used by thousands of scientists throughout the world.