Ben Ho Park, MD, PhD
Associate Professor, Oncology
The Sidney Kimmel Comprehensive Cancer Center
Johns Hopkins University School of Medicine
2013-2014 BCRF Project:
(The J.C. Penney Award)
The overarching goal of Dr. Park’s research program is to identify and validate genetic targets in the PI3Kinase pathway for breast cancer therapy and translate these findings for clinical benefit. His team continues to make significant progress with their research.
An ongoing unmet need is to exploit mutant PIK3CA for cancer therapy, as PI3K inhibitors have had limited success in early phase clinical trials. An underlying reason for this may be that current PI3K inhibitors are not specific for mutant PIK3CA, and that different PIK3CA mutations activate oncogenic pathways in distinct ways. In addition, Dr. Park’s team has recently shown that accurate assessment of a patient’s PIK3CA mutation status is problematic due to tumor heterogeneity. Understanding mechanisms of mutant PIK3CA oncogenic pathway activation along with improved diagnostics would greatly impact the ability to select appropriate targeted therapies for cancers with PIK3CA mutations. Thus the long term goal of this research is to elucidate how common PIK3CA mutations distinctly activate critical pathways, then target these interactions for therapy and accurately identify patients whose cancers harbor these mutations. The specific hypothesis to be tested is that common “hotspot” mutations in PIK3CA have different requirements for oncogene function that can be exploited for therapeutic gain. The underlying rationale of Dr. Park’s approach is to use next generation genetic models and methods to uncover distinct mechanisms used by different PIK3CA mutations and to target these pathways with existing therapies and drugs in clinical trials allowing for near term impact.
Dr. Park’s team continues continue to make significant progress with their proposed studies. They have shown that HER3 is a critical mediator of cell growth and signaling imparted by the PIK3CA H1047R mutation but much less so for the PIK3CA E545K mutation. In turn, we are still investigating whether other receptors preferentially partner with selected mutations. Excitingly, many of these receptors have approved drugs against them, or are in late stage clinical trials suggesting that the researchers may be able to target breast cancers with existing therapies and therapies that are near FDA approval. This is the basis of their second goal, and their preliminary data suggests that this is feasible as they have made significant progress in demonstrating druggable pathways are differentially utilized by different mutations. Finally, we are accruing patients for our third objective. For this aim, their goal is to compare and improve upon the way we identify PIK3CA mutations in patients with metastatic disease. Knowing now that tumor heterogeneity is an enormous problem for breast cancer that leads to mutations being present versus absent in different metastatic sites, they now realize that biopsy of a single metastatic site may miss PIK3CA mutations present in other disease areas of the body. As such, they are collecting blood and metastatic biopsies simultaneously to demonstrate that querying the blood for PIK3CA mutations using a new technology called droplet digital polymerase chain reaction (ddPCR) can detect all mutations from all sites of metastatic disease. This is because all cells, including cancer cells, shed DNA into the blood, which therefore allows researchers to find mutations in the blood that originate from any metastatic site since blood will act as a global “reservoir”. Dr. Park’s team has already shown their ability to detect these mutations in blood and continue to move this aim forward to definitively prove that blood or “liquid” biopsy can replace the need for tissue biopsy for PIK3CA mutation detection.
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.