Dr. Robert C. Bast, Jr., is Director of Translational Research Career Development and Harry Carothers Wiess Distinguished University Chair for Cancer Research at The University of Texas MD Anderson Cancer Center in Houston. Dr. Bast coordinates the Physician-Scientist and K12 Clinician-Investigator programs to develop careers of junior faculty at MD Anderson.
Dr. Bast’s research has focused on translational approaches to the biology and management of ovarian cancer. He has addressed three of the major factors that contribute to poor outcomes for ovarian cancer patients: late diagnosis, drug resistance and the persistence of dormant cancer cells. This work has appeared in more than 700 original articles, reviews, commentaries and editorials.
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 ultrasound exams that has proven sufficiently specific to be cost effective and that has detected early stage disease 70% of patients. As CA125 is expressed by only 80% of ovarian cancers, his group has evaluated >120 candidate blood biomarkers to identify 3 additional blood tests that detect cases missed by CA125. A new trial is planned to evaluate rising values of the 4 biomarkers in combination to trigger ultrasound exams. 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. Autoantibodies against CTAG1 and Interleukin-8 also promise to provide much needed lead time.
With regard to overcoming drug resistance, Dr. Bast’s group has identified alt-induced kinase 2 (SIK2) that regulates resistance to three of the drugs used to treat ovarian cancers including paclitaxel, carboplatin and PARP inhibitors. Inhibition of SIK2 with a new drug GRN300 enhances sensitivity to each if these agents. In collaboration with Greenfire Bio, a phase I trial of GRN300 is underway.
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. Of the 41 graduates of the physician-scientist program, 83% have been awarded their first major grant (NIH R01 or equivalent). Of the 32 graduates of the K12 clinician-investigator program, 13 have conducted studies leading to FDA approval of drugs or a change in national practice guidelines. 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 served as the first chair of the Foundation’s Scientific Advisory Committee from 1993 to 2018. He has served on multiple NIH study sections and committees and chaired the Oncologic Drugs Advisory Committee of the Food and Drug Administration.