Targeting PLK-1 for Treating MYC-Driven Lymphomas
Abstract
The proposed study will address the Fiscal Year 2018 (FY18) Peer Reviewed Cancer Research Program (PRCRP) topic area Lymphoma. MYC-driven lymphoma is a group of aggressive lymphomas where an elevated level of MYC plays an important role in the lymphomagenesis and tumor progression. MYC-driven lymphoma accounts for a large proportion of aggressive B-cell lymphomas and affects both children and adults. Most patients with MYC-driven lymphoma present with an aggressive clinical course and respond poorly to concurrent conventional therapies. There is an urgent unmet need for developing novel therapeutic strategies for these diseases. Based on our recent discovery of PLK-1 as a key kinase mediating MYC oncogenic function, the proposed study aims to determine if PLK-1 can serve as a promising therapeutic target for better treatment of MYC-driven lymphoma. The study will also develop a practical PLK-1 targeting strategy that can be quickly advanced to clinical trials in the next few years. If successful, the proposed study would have a significant impact on the clinical management of patients with aggressive B-cell lymphoma. The current study will address issues within the FY18 PRCRP Military Relevance Focus Area Gaps in cancer prevention, early detection/diagnosis, prognosis, treatment, and/or survivorship that may affect the general population but have a particularly profound impact on the health and well-being of military Service members, Veterans, and their beneficiaries. Non-Hodgkin lymphoma (NHL) is one of the most common types of cancer in the United States and ranks No.7 in the cancer incidence among patients of U.S. Veterans (2007 Survey). More importantly, chemicals such as Agent Orange as well as ionizing radiation exposure have been linked to NHL. Other risk factors with military relevance linked to NHL include infections, such as malaria, that weaken the immune system, and exposure to certain toxins and drugs, such as chemo-reagents used to treat other cancers. In NHL, MYC is one of the most commonly mutated oncogenes and is closely associated with aggressive clinical course, refractory disease, and inferior clinical outcome. Therefore, the development of effective therapeutic strategies will largely benefit populations with MYC-associated hematological malignancies, including military Service members, Veterans, and their beneficiaries.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910509
Entities
People
- Kai Fu
Organizations
- United States Army
- University of Nebraska Medical Center