2019 Grantee: Wantong Yao, MD, PhD
MD Anderson Cancer Center
Research Project: Targeting Syndecan1 in Pancreatic Cancer
Award: 2019 Pancreatic Cancer Action Network Translational Research Grant
Award Period: July 1, 2019 – June 30, 2022
Dr. Yao is an assistant professor at University of Texas MD Anderson Cancer Center. Dr. Yao obtained her PhD degree from Fudan University, China, where she focused her research on understanding the molecular mechanisms for pancreatic cancer (pancreatic ductal adenocarcinoma) development and progression, specifically on the regulation and function of cytoskeleton remodeling.
The clinical challenges she faced during her clinical training specialized in pancreatic cancer surgery in Shanghai Cancer Center further motivated her to pursue further postdoctoral training in Dr. Giulio Draetta’s lab in MD Anderson Cancer Center with the goal of discovering new mechanisms, biomarkers and vulnerabilities as drug targets for pancreatic cancer. Her research work during this period led to the discovery of syndecan-1 (SDC1), a cell surface proteoglycan linked to cytoskeleton, as an important functional protein activated by mutant KRAS. This work was funded by the Pancreatic Cancer Action Network Pathway to Leadership Grant in memory of Carina Rogerson. Following the establishment of her independent lab in 2018, Dr. Yao continues to explore the therapeutic potential of SDC1 and explore additional key targetable nodes for the treatment of pancreatic cancer.
The most common type of pancreatic cancer, pancreatic ductal adenocarcinoma, is almost universally driven by genetic mutations in KRAS, designating it an ideal therapeutic target. However, no effective drugs directly inhibiting mutant KRAS have reached the clinic.
Dr. Yao and her colleagues’ recent work has established that the protein syndecan-1 (SDC1) plays a critical role in helping pancreatic cancer cells survive and grow. Furthermore, they have shown that SDC1 is tightly regulated by mutant KRAS, and this relationship is required for pancreatic cancer progression and maintenance. The team’s studies to determine why the mutant KRAS-SDC1 relationship is needed for pancreatic cancer uncovered that SDC1 is crucial for a process called macropinocytosis, by which pancreatic and other tumors scavenge “food” to fuel their growth.
It stands to reason that blocking the food supply of pancreatic cancer cells by inhibiting SDC1-triggered macropinocytosis may result in cell death. Thus, in Dr. Yao’s effort to target this SDC1 driven cancer mechanism, she and her team developed therapeutic antibodies to target SDC1. Building on this substantial work, the overarching objective of this proposed research is to further characterize the role of SDC1 in the metabolic reprogramming of pancreatic cancer cells and to explore the potential of SDC1 as a therapeutic target with its antibody. These studies will provide important new data regarding the potential of SDC1 to serve as a therapeutic target for pancreatic cancer in the clinic.