Ben Ho Park, MD, PhD
Associate Professor, Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD
2009-2010 BCRF Project:
Targeted cancer therapies against mutated genes provide the best chance for developing highly effective drugs with minimal side effects. Accordingly, the discovery of mutations at high frequency within a gene called PIK3CA in human breast cancers, has led to an intense search for agents that can specifically target cancer cells carrying these mutations.
In preliminary work, Dr. Park and colleagues have identified critical pathways that are activated and lead to growth of breast cancer cells due to these PIK3CA mutations. Moreover, they have used a cellular genetics based approach to identify drugs that specifically target these aberrant pathways. They have made significant progress over the past year, including the publication of results describing the characterization of genetically modified human breast cell lines whereby the researchers introduced pathologic mutations into the cancer gene PIK3CA and showed that this confers sensitivity to the FDA approved drug lithium. They have also characterized the effects of two additional genetic alterations that occur in human breast cancers: loss of the gene PTEN and mutation of the AKT1 gene. Their studies demonstrated that these gene alterations are not equivalent to PIK3CA mutations in biological phenotypes or sensitivity to lithium.
They have initiated new experiments to try and further elucidate the mechanism of how mutations in the PIK3CA oncogene lead to lithium sensitivity by mutating an effector gene called GSK3beta. In addition, successful laboratory model experiments using lithium to treat mutant PIK3CA cancers have been completed, and further work with other mutant PIK3CA breast cancers are ongoing. Finally, from preclinical data, the scientists are now designing a clinical trial based upon this work. It is hoped that this study will provide the underpinnings for future targeted therapies against the many breast cancers that harbor mutations in PIK3CA.
Bio:
Dr. Park is an Associate Professor of Oncology with a Joint Appointment in the Whiting School of Engineering. He grew up in Saginaw, Michigan and attended The University of Chicago receiving his A.B. degree in Biology in 1989. He then pursued dual degree training at The University of Pennsylvania School of Medicine where he received both his MD and PhD degrees in 1995. Dr. Park then trained in Internal Medicine and Hematology/Oncology at The Hospital of The University of Pennsylvania prior to coming to Johns Hopkins where he completed a post-doctoral fellowship in cancer genetics in the laboratory of Drs. Ken Kinzler and Bert Vogelstein.
In 2002, Dr. Park joined the faculty at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in the Breast Cancer Research Program. His lab utilizes sophisticated genetic models to identify, validate and develop targeted therapies for breast cancer. Currently the lab is focused on the PI3 Kinase/AKT signaling pathway, based on the lab's initial finding that the PIK3CA gene is mutated at high frequency in human breast cancers
Dr. Park remains actively involved with all aspects of biomedical research training including teaching of graduate and medical students, post-doctoral fellows, interns, residents and clinical fellows. In addition, Dr. Park continues clinical duties including attending on the inpatient oncology service and seeing breast cancer patients in the outpatient setting.
