Robert C. Bast Jr., M.D.
Dr. Robert C. Bast, Jr., is Vice President for Translational Research and Harry Carothers Wiess Distinguished University Chair for Cancer Research at The University of Texas MD Anderson Cancer Center in Houston. His office coordinates institutional shared resources, programs to develop multi-investigator grants and the career development of physician-scientists and clinician-investigators. They write and administer the NCI CCSG “Core” grant upon which MD Anderson’s designation as an NCI Comprehensive Cancer Center is based.
Dr. Bast’s research has focused on translational approaches to the biology and management of ovarian cancer. He has addressed two of the major factors that contribute to poor outcomes for ovarian cancer patients: late diagnosis and the persistence of dormant, drug resistant cancer cells. This work has appeared in more than 500 original articles.
Dr. Bast developed the first murine monoclonal antibodies against ovarian cancer and discovered CA125, the first generally useful ovarian cancer blood biomarker for monitoring ovarian cancer that has contributed to the care of hundreds of thousands of women worldwide. Dr. Bast has worked with Dr. Karen Lu to conduct a two-stage screening study, where rising CA125 triggers transvaginal sonography that has proven sufficiently specific to be cost effective and that has detected early stage disease in the majority of patients. As CA125 is expressed by only 80% of ovarian cancers, his group has evaluated >110 candidate blood biomarkers to identify HE4 and CA72.4 that detect cases missed by CA125. Anti-TP53 autoantibodies can also detect additional CA125 deficient cases and can be elevated 8 months prior to CA125 when it rises and 22 months prior to diagnosis when it does not. Currently, they are evaluating other autoantibodies as biomarkers for early detection and conducting a clinical screening trial with multiple biomarkers.
With regard to overcoming drug resistance, Dr. Bast’s group has identified several kinases that regulate paclitaxel sensitivity through effects on centrosomes and microtubules, including SIK2, CDK5, IkBkB, STK39 and PFKB2. In collaboration with Arrien Pharmaceuticals, they are studying a small molecule inhibitor of SIK2 that enhances paclitaxel sensitivity and that will enter clinical trials this year.
Dr. Bast’s group has identified ARHI (DIRAS3), an imprinted tumor suppressor gene that is downregulated in 60% of ovarian cancers. Re-expression of ARHI blocks cell growth, inhibits motility, induces autophagy and establishes tumor dormancy. By re-expressing ARHI from a doxycycline inducible promoter in ovarian cancer xenografts, Dr. Bast’s group has developed the first inducible model for tumor dormancy in ovarian cancer, permitting evaluation of novel anti-autophagic therapy to eliminate dormant ovarian cancer cells. These approaches are being extended to clinical trials in ovarian cancer patients with residual disease at “second look” surgery.
Dr. Bast has mentored more than 70 undergraduates, graduate students, medical students, postdoctoral fellows and visiting investigators in his laboratory. He has also mentored more than 70 physician–scientists and clinician–investigators on the faculty at MD Anderson. He has edited the textbook Cancer Medicine, established a series of books on Translational Cancer Research and is preparing a primer for the series.
Dr. Bast has served on advisory groups for 12 US Cancer Centers, the Cancer Center Karolinska in Stockholm, Ovarian Cancer Action in London, the Deutsche Krebshilfe in Bonn, Germany and the Berlin Institute of Health. He is a founding member of the Board of Directors of the V Foundation and heads the Foundation’s Scientific Advisory Committee. He has served on multiple NIH study sections and committees and chaired the Oncologic Drugs Advisory Committee of the Food and Drug Administration.