Gordon B. Mills, MD, PhD
Chair and Professor, Department of Systems Biology
Head, Kleberg Center for Molecular Markers
Wiess Distinguished University Chair In Cancer Research
University of Texas MD Anderson Cancer Center
2013-2014 BCRF Project:
Dr. Mills and colleagues have generated a laboratory model of spontaneous breast cancer formation driven by specific alterations of the Autotaxin-Lysophosphatidic Acid Signaling Pathway (ATX/LPA axis) in mammary glands. The establishment of a transplantation procedure in which fragments of these tumors are seeded and grown in laboratory models is giving the investigators the opportunity of probing the heterogeneity of the disease to better understand its complexity. Currently, Dr. Mills and his group are studying how these tumors adapt and grow in the laboratory models that are exposed to different dietary stimuli. They have found that some of these tumors were capable of causing a dramatic drop in body weight when transplanted in models. The total loss of body fat and significant reduction of muscle mass were consistent with the models undergoing wasting syndrome (cachexia) development, a poorly understood multifactorial condition correlated with high mortality rate and poor quality of life in cancer patients. Dr. Mills’s efforts are not only focused on understanding the dynamics of this phenomenon but also on discovering possible treatment options that can improve the condition.
The versatility of this breast cancer model is providing a wealth of experimental opportunities and preclinical observations with potential for translation to actionable clinical practice. With BCRF support, Dr. Mills hopes to shed more light on different aspects of breast cancer biology and to discover new therapeutic approaches that can benefit breast cancer patients.
Stopping very aggressive breast cancers such as inflammatory breast cancer, subsets of triple negative breast cancer, and other rapidly progressive breast cancers requires knowledge of their "wiring" of networks that disperse information throughout the cancer cell. By studying these networks, Dr. Mill and his colleagues have devised potential new avenues to attack aggressive cancer cells when they are moving, by interfering with proteins that regulate cell motility. Moreover, they are designing and testing simple synthetic devices that simulate human organs to test small aggressive cancers for their potential to spread to distant sites before they ever do. In this manner, the researchers hope to be able to guide therapies that prevent metastases from occurring.
Dr. Mills earned his MD and his PhD in biochemistry from the University of Alberta. From 1985 to 1994, Dr. Mills was a member of the faculty of the University of Toronto, rising to the rank of Associate Professor in the departments of Obstetrics and Gynecology, Immunology, and Clinical Biochemistry. He was an active staff member and director of Oncology Research at the Toronto Hospital during this time.
In 1994, Dr. Mills was recruited to The University of Texas MD Anderson Cancer Center, where he holds the rank of professor with joint appointments in Systems Biology, Breast Medical Oncology and Immunology; serves as chairman of the Department of Systems Biology; head of the section of Molecular Therapeutics and holds the Ann Rife Cox Chair in Gynecology. Dr. Mills is co-Director of the Kleberg Center for Molecular Markers and director for the Gita and Ali Saberioon Molecular Markers building.
With more than 300 publications, Dr. Mills has authored papers in such prestigious journals as Nature, Cell, Oncogene, Nature Genetics, Nature Medicine, Nature Cell Biology, Nature Cancer Reviews, Cancer Research, Proceedings of the National Academy of Sciences and Clinical Cancer Research. A testament to the quality of his research, Dr. Mills' work in ovarian cancer, breast cancer and tumor immunology has been continuously funded by major peer-reviewed grants for over 20 years. He serves as principal investigator or project investigator on ten national peer review grants including NIH/NCI SPOREs and PPGs, Department of Defense, and Komen Foundation grants, and collaborator on multiple other national peer-reviewed grants.
Dr. Mills has made significant contributions to the understanding of ovarian tumorigenesis, including the identification and development of lysophosphatidic acid (LPA) and sphingosine 1 phosphate (S1P) as possible markers for early-stage ovarian cancer and as a potential targets for therapy. He also has played a major role in increasing our understanding of the genetic aberrations in the phosphatidylinositol 3 kinase/PTEN/AKT pathway, forwarding this cascade as a major target for the therapy of multiple types of cancer. Dr. Mills has also extensively explored the genomics and genetics of ovarian and breast cancer identifying and characterizing a number of potential oncogenes and tumor suppressor genes including ARHI, Rab25, EVI1 and PKCi. These are being explored both as markers and targets for therapy.
Dr. Mills is the holder of more than 20 patents related to novel technologies and molecular markers. He was a co founder of an early diagnostics company. He currently sits on the scientific advisory boards of multiple different companies and venture capital groups. Based on his expertise in technology development, he is the head of the MD Anderson Cancer Center Technology Review Committee.
Dr. Mills now heads the Kleberg Center for Molecular Markers. This Center holds the responsibility for developing personalized molecular medicine at the MD Anderson Cancer Center. Specifically, this center will implement a series of novel technologies to for the first time explore the genetic changes and their consequences at the DNA, RNA and protein levels in human tumors. This information will be used to identify patients at high risk for tumor development so they can be triaged to early screening and chemoprevention, identify markers to use in early screening, and to determine approaches to ensure that patients receive the most effective and least toxic therapies targeting the underlying genetic aberrations in tumors.
Dr. Mills is the inaugural chair of the Department of Systems Biology. The mission of the Department of Systems Biology to understand how a process, a cell, a group of cells, or an organism works at a global level and how different components of the process cooperate to attain the "correct" functional outcome. It is now recognized that component-by-component analysis is not sufficient for the study of signal transduction, gene regulatory and biochemical networks, oncogenic transformation, and other processes in which many genes and proteins interact. Understanding the dynamics of such systems, both qualitatively and quantitatively, and constructing mathematical models with robust predictive capabilities will be necessary for the realization of the promise of personalized molecular medicine and the efficient implementation of targeted therapeutics.
In December 2013 at the world-renowned San Antonio Breast Cancer Symposium, Dr. Mills will receive the Brinker Award for Scientific Distinction in Basic Science for his significant contributions to breast cancer research, which have been essential to advancing our understanding of the key processes that drive breast cancer’s initiation, progression and response to therapy. Dr. Mills has championed a cancer systems biology approach to understand the impact of genomic aberrations on complex signaling networks at the proteomic (protein) level, with the goal of individualizing cancer diagnosis and treatment.