PI: Sam S. Yoon, MD
630 W. 168th Street, 17-409
New York, NY 10032
Dr. Yoon’s research examines the tumor microenvironment and cancers stem-like cells in order to develop new therapies for sarcomas and gastric cancer. The efforts of his laboratory are directed toward translational research and clinical trials, and currently include two main projects.
Role of cancer stem-like cells in gastric cancer metastasis and chemotherapy resistance
Gastric cancer is a leading cause of cancer death worldwide. Most patients who succumb to these tumors do not die from their primary tumors but from metastatic disease, which commonly occurs in the liver and peritoneal cavity. Many of these patients do not have identifiable metastatic disease at the time of diagnosis, but harbor radiologically occult micrometastases that ultimately grow to lethal sizes.
Dr. Yoon’s lab has investigated several pathways which play an important role in gastric cancer stem-like cells (CSCs) in terms of tumorigenesis, metastasis, and chemotherapy resistance. These pathways include Hedgehog, RhoA, Rac1, KMT2C, and most recently KRAS. These studies were reported in three Clinical Cancer Research and two Molecular Cancer Research articles. In collaboration with Dr. Sandra Ryeom (University of Pennsylvania), we developed a genetically engineered mouse model of gastric cancer which recapitulates human disease in terms of nodal and distant metastases (Till J et al. Cancer Res 2017:77:5349-59, PMID 28760854). These studies have led to two recent grants from the DeGregorio Family Foundation and Stand Up To Cancer. Current studies are examining the use of patient tumor-derived organoids in predicting response to neoadjuvant chemotherapy, and the use of state-of-the-art diagnostics to detect clinical silent early gastric cancers.
Hypoxia-inducible factors (HIFs) and vascular endothelial growth factor A (VEGF-A) in sarcoma progression, metastasis, and radiation response
Soft tissue sarcomas arise in about 13,000 persons in the United States each year, and about 40 percent of patients die of either locoregional recurrence or distant metastasis. As sarcomas and other solid tumors outgrow their blood supply, hypoxia (or oxygen deprivation) stabilizes hypoxia-inducible factors 1α and 2α (HIFs), which bind to ARNT (aka HIF-1β) and drive the transcription of hundreds of genes. Some of these genes, including vascular endothelial growth factor A (VEGF-A) mediate tumor angiogenesis, while others play a role in tumor invasion (e.g., c-MET) and metastasis (e.g., FOXM1).
VEGF-A is likely the most important factor driving tumor angiogenesis. HIFs and VEGF-A are upregulated in sarcomas, and increasing levels of these proteins correlate with the extent of disease and metastasis. Anti-VEGF-A agents effectively suppress tumor angiogenesis and growth in many human cancers, but VEGF-A inhibition can also increase hypoxia, leading to enhanced tumor invasion and metastasis.
Dr. Yoon and colleagues found that that combining VEGF-A inhibition with radiation therapy synergistically inhibits the growth of sarcomas in mouse models (Kirsch DG et al. Nature Med 2007:13:992-7; Yoon SS et al. Int J Radiat Oncol Bio Phys 2009:74:1207-16, PMID 19545786). This led to a phase II clinical trial of bevacizumab (an anti-VEGF-A antibody) and radiation for sarcomas that validated this combination in patients with sarcomas (Yoon SS et al. Int J Radiat Oncol Bio Phys 2011:81:1081-90, PMID 20932656). This trial formed the bases for a phase III randomized trial that was recently completed by the COG and NRG cooperative groups. Gene expression analysis of tumors from the phase II clinical study revealed that upregulation of HIFs and HIF-target genes is a likely mode of resistance to bevacizumab. This in turn led to a two-PI NIH/NCI R01-funded research project with Dr. M. Celeste Simon (University of Pennsylvania) examining the role of HIFs and VEGF-A in sarcomagenesis, metastasis, and radiation response. Following a continuing renewal of this R01 grant, Dr. Yoon’s lab is currently examining the role of HIFs in regulating the response of sarcomas to anti-PD-1 immunotherapy.
Current Lab Members
Changhwan Yoon, Ph.D., Associate Research Scientist
Former Lab Members
Clinical Research Fellows:
- 2019-2021: Jun Lu, M.D, Ph.D., Surgeon, Fujian Medical University Union Hospital, Fujian, China
- 2018-2020: Jian-xian Lin, M.D, Ph.D., Surgeon, Fujian Medical University Union Hospital, Fujian, China
- 2015-2017: Kevin Chang, M.D., General Surgery Resident, Brigham and Women’s Hospital, Boston, MA
- 2014-2016: Jun Ho Lee, M.D., Ph.D., Surgeon, Samsung Medical Center, Seoul, Korea
- 2013-2015: Soo-Jeong Cho, M.D., Ph.D., Gastroenterologist, National Cancer Center, Gyeonggi, Korea
- 2012-2014: Do Joong Park, M.D., Ph.D., Surgeon, Seoul National University Bundang Hospital, Seongnam, Korea
- 2011-2013: Benjamin Schmidt, M.D., General Surgery Resident, University of Connecticut
- 2008-2010: Ugwuji Maduekwe, M.D., M.M.Sc., General Surgery Resident, Massachusetts General Hospital
- 2006-2008: Moritz Koch, M.D., Surgical Oncologist, University of Heidelberg, Heidelberg, Germany
- 2004-2006: Sung-Hwan Kim, M.D., Ph.D., Radiation Oncologist, St. Vincent Hospital, Suwon, Korea
- 2010-2012: Hae-June Lee, Ph.D., Korea Institute of Radiological and Medical Sciences, Seoul, Korea
- 2008-2010: Yoon-Jin Lee, Ph.D., Korea Institute of Radiological and Medical Sciences, Seoul, Korea
- 2017-2018: Brandon Yi, B.S., University of Chicago
- 2016: Emily Ryeom, Massachusetts Institute of Technology
- 2010-2012: Alexia Zhang, B.S., Wellesley University
- 2008-2010: Daniel Karl, B.S, M.S., University of Chicago
- 2004-2006: Namali Fernando, B.S., Wellesley University
- 2004-2006: Lila Gollogly, B.S., Harvard University
2003-2004: Kara Detwiller, B.S., Wellesley University