Brian A. Van Tine, MD, PhD
Assistant Professor of Medicine, Sarcoma Program Director, Washington University in St. Louis
2013 Sarcoma Foundation of America Research Grant Recipient: “A Metabolomic Approach to Targeting ASS1 Deficient Sarcomas”
2014 Sarcoma Foundation of America Research Grant Recipient: “Targeting the Pentose Phosphate Pathway for the Treatment of Synovial Sarcoma”
2017 Sarcoma Foundation of America Research Grant Recipient: “Targeting the alterations of Lipid Metabolism in ASS1 Deficient Sarcomas to Induce Synthetic Lethality”
PLEASE DESCRIBE THE FOCUS OF THE RESEARCH PERFORMED IN YOUR LAB.
I am an Assistant Professor of Medicine in the Department of Medicine at Washington University in St. Louis, Missouri, USA, where I am the Sarcoma Program Director at the Alvin J. Siteman Cancer Center. I received my Bachelors of Science degree from the Departments of Chemistry and Biochemistry at The University of Arizona in 1995. I completed my MD and PhD degrees at the University of Alabama at Birmingham in 2005. After completing my MD, PhD, I came to Washington University in St. Louis/Barnes – Jewish Hospital, where I did my Internal Medicine Residency and Medical Oncology Fellowship. I am the sarcoma medical oncologist for the mid-west region surrounding St. Louis, focusing my efforts on translating basic science observations to clinical trials. My laboratory is dedicated to understanding the metabolomics deficiencies found in sarcomas, as they can be therapeutically targeted. My laboratory has identified Argininosuccinate Synthetase 1 (ASS1) deficiencies in sarcomas that can be treated with pegylated-arginine demiminase. Funding supported by the SFA has allowed for the development of biomarker driven metabolic therapies for all sarcomas and is now moving into clinical trial. In addition, funding for SFA has supported the identification of a metabolic deficiency in synovial sarcoma that can also be therapeutically exploited. This finding has resulted in a clinical trial that is opening soon at Washington University in St. Louis.
WHAT HAS INSPIRED YOU TO RESEARCH SARCOMA?
During my clinical fellowship, I met a patient who changed my life. She was a young, smart, and articulate woman who not only had a rhabdomyosarcoma on her heart, but she was also 22 weeks pregnant. This began a life altering journey that began at a bedside in an ICU. While treating my first sarcoma patient, I began to realize that this is a field with untapped potential for clinical impact. Given my PhD background in cervical and breast cancer research, on that day I decided that I was going to devote my life’s work to doing something about this dreaded disease. Since then, every patient I have met and had the opportunity to learn from has taught me that much more is needed to make a difference.
PLEASE SHARE A BIT ABOUT THE PROJECT THAT WAS FUNDED BY YOUR SFA RESEARCH GRANT AWARD.
My present work involves the understanding of the metabolism of sarcomas. We are the first to identify that argininosuccinate synthetase 1 (ASS1 ) is silenced in ~90% of sarcomas which renders them susceptible to arginine deprivation therapies since they are not able to synthesize the amino acid arginine. We are presently working to understand the changes that occur when arginine is depleted from cells that are ASS1 deficient using global metabolomic approaches. We were able to silence a gene called pyruvate kinase M2, the protein necessary, but not sufficient, for the activation of the Warburg effect. This target of amino acid deprivation based therapies results in a metabolic shift to glutamine dependency and allows glutaminase inhibitors to work. This has led to the identification of the first duel metabolic therapy using arginine deiminase and a glutaminase inhibitor.
HOW HAS FUNDING FROM THE SARCOMA FOUNDATION OF AMERICA HELPED IN YOUR RESEARCH EFFORTS?
The funding from the Sarcoma Foundation of America was vital in allowing us to do the exploratory research that was needed for clinical translation and larger grant funding. Funding from SFA grants has not only benefit my research efforts, but has allowed for the development of two clinical trials to benefit sarcoma patients. Obtaining funding for fundamental research in sarcoma is difficult when you have to compete with breast cancer and lung cancer researchers. Having a focused source for funding from the SFA allows for the development of the research that is needed to help the sarcoma patients. Hopefully, the continued support from SFA of not only my research, but the research of the other sarcoma investigators, will quickly transform the treatment of sarcoma from toxic chemotherapy to novel therapies that are highly effective and curative.