Calls Now Open
2027 Scholar-Innovator and ADDF-Harrington
Oncology, Immunology, Metabolic
Targeting mRNA-Specific Translation in Cancer
2024 Harrington Scholar-Innovator
Dr. Hsieh has two reasons for choosing to pursue prostate cancer research. The first is that every year in the United States castration-resistant prostate cancer (CRPC) affects roughly 230,000 men and results in about 30,000 deaths. The second reason is more personal: in 2009, metastatic prostate cancer claimed the life of Dr. Hsieh’s father-in-law.
For the past decade, Dr. Hsieh’s lab has been studying the interaction between mRNA translation initiation—the process through which the genetic information encoded in messenger RNA is used to build proteins in cells—and androgen receptor (AR) signaling, a crucial pathway involved in prostate cancer development and progression.
Dr. Hsieh and his colleagues found that decreased AR activity is commonly seen in CRPC patients. This decrease leads to a corresponding increase in translation initiation, specifically through a potentially cancer-causing interaction between two cellular proteins: eIF4E and eIF4G. The team is exploring elF4E inhibitors as a potential therapeutic strategy for prostate and other cancers.
After using AI to help screen 2.7 million compounds, Dr. Hsieh’s team identified a promising drug candidate. With the support of Harrington Discovery Institute, Dr. Hsieh and his team are poised to conduct optimization of this lead compound, and in vitro and in vivo testing for efficacy in prostate and other forms of cancer, including breast, lung, and bladder.
“We think that this is an untapped opportunity,” Dr. Hsieh says. “Given the clinical need and the discovery of a lead compound, our program is poised to make a discovery with therapeutic impact.”
"Current therapies for metastatic disease can extend life, but our vision of resounding success is a cure."