Exosome-Mediated Thrombosis in Pancreatic Cancer
Abstract
Career Goals: My career goal is to become an independent investigator at the forefront of translational cancer research, with a strong focus on pancreatic cancer and its progression into metastatic cancer. In my future independent career, I envision tackling unanswered questions of the biology of cancer dissemination and identifying novel therapies to prevent cancer progression and complications. The Horizon Award will allow me to achieve these goals through different means. First, it will allow the further development of my research niche on coagulation disease in pancreatic cancer patients. This will involve the consolidation and expansion of a technical skillset that will prove essential for future independent projects. Second, I will engage in collaborative work with other researchers and clinicians, who will provide specialized training, sharpen critical thinking, and encourage the development of independent research directions. Furthermore, this award will promote the dissemination of the results via publications and scientific conferences, promoting my affirmation as an expert in the field of pancreatic cancer and coagulation. Finally, this award will support application to larger-scale fellowships that will increase my competitiveness for independent group leader positions. Project Rationale: Pancreatic cancer remains a major cause of death in the U.S. According to the American Cancer Society, more than 50,000 people will be diagnosed with pancreatic cancer by the end of 2019 and only 9.3% of those patients will be alive 5 years after diagnosis. Active duty Service members and Veterans might be at higher risk of developing pancreatic cancer, due to exposure to radiation during Service, according to the U.S. Department of Veterans Affairs. The second leading cause of death in pancreatic cancer patients is the formation of clots in blood vessels, a phenomenon known as thromboembolism (TE). TE affects at least one-third of patients with pancreatic cancer and causes more than 40% of deaths not associated with cancer progression. Currently, it is not possible to predict the occurrence of TE events. Additionally, current therapies can increase bleeding risk, posing a serious threat to high-risk patients. Hence, further research is needed to discover new ways to identify and treat pancreatic cancer patients at high risk of TE. Exosomes are nanoscopic vesicles that mediate communication between different cells through transfer of their cargos. Cancer-derived exosomes can be released in the bloodstream and support cancer progression and spreading to other organs. Prior evidence suggests that they might also initiate TE in cancer patients, but the underlying mechanisms remain unknown. This project aims to understand the role of exosomes in the onset of TE in pancreatic cancer patients by addressing the following questions: (1) To what degree do exosomes initiate TE events at different stages of cancer progression? (2) How do exosomes activate clotting and how can this process be blocked? (3) Can blood exosomes be used as a “fingerprint” for patients at high risk of TE? By answering to these questions, we will obtain a better understanding of the role of exosomes in pancreatic cancer-associated TE. This will lead us to discover and test new therapies to block TE caused by exosomes, which will be mostly beneficial for patients experiencing incident or recurring TE. Moreover, we will assess whether exosomes derived from the blood of cancer patients can predict TE events before their occurrence. This will be tested in a cohort of pancreatic cancer patients recruited at Memorial Sloan Kettering Cancer Center. Hence, our results will be applicable to the clinic immediately at the end of our study, in 2 years’ time. If an association between exosome fingerprint and TE is found, then blood exosomes can be used in the clinic as a non-invasive “liquid biopsies” to identify patients at high risk of havin
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010263
Entities
People
- Serena Lucotti
Organizations
- United States Army
- Weill Cornell Medicine