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Implications of stress-induced LPAR4 expression in lung and pancreatic cancers

Institution: University of California, San Diego
Investigator(s): Chengsheng Wu,
Award Cycle: 2019 (Cycle 29) Grant #: T29FT0343 Award: $180,996
Subject Area: Cancer
Award Type: Postdoctoral Fellowship Awards

Initial Award Abstract
In 2018, lung and pancreatic cancer accounted for approximately 200,000 cancer-related deaths in the United States. A common risk factor for these two cancers is cigarette smoking, which can account for ~80% of lung and ~30% of pancreatic cancers. Although most lung and pancreatic cancers are initially responsive to therapy, these tumors eventually stop responding, allowing them to grow and spread. In order to make tumors more sensitive to therapy and for the effects of therapy to remain effective for longer, it is critical to understand the molecular pathways cancer cells use to evade the effects of therapy. My project focuses on a protein located on the surface of some cancer cells named lysophosphatidic acid receptor 4 (LPAR4). Lung and pancreatic cancer patients with high levels of LPAR4 show shorter survival compared with patients who have low LPAR4 levels. Interestingly, LPAR4 is only detected when the cancer cells are challenged by unfavorable growth conditions, such as poor access to nutrients or treatment with cancer therapy. Once cancer cells gain LPAR4, they become more aggressive, more likely to spread or metastasize, and they are able to ignore the effects of therapy. These findings suggest that targeting LPAR4 might represent a new way to sensitize lung and pancreatic cancers to the effects of therapy. The first goal of my project is to better define how LPAR4 contributes to lung and pancreatic cancer progression. To do this, I will ask how cancer cells turn on LPAR4 as a way to cope with stress, and I will investigate how they take advantage of LPAR4 to become drug resistant. My second goal is to develop and test new anti-cancer strategies targeting LPAR4 as a new way to halt tumor progression and sensitize tumor cells to the effects of therapy. By understanding the functions of LPAR4 in lung and pancreatic cancer cells, my project should identify new therapies for these two cancer types with strong links to cigarette smoking.