Novel Driver in Lung Adenocarcinoma and Its Therapeutic Potential
Abstract
Lung cancer is one of the most common cancers worldwide. Compared with other major lethal cancers, patients with lung cancer suffer from lack of effective therapeutic intervention. Thus, new approaches for the rapid identification and functional validation of the genetic and/or epigenetic alterations associated with lung cancer development are urgently needed. The major goals of this proposal are to characterize a newly identified potential driver gene of lung cancer using genomic studies as well as to test the therapeutic potential of targeting this novel driver gene. Our proposal is highly relevant to focused areas of research, as PEA15 is highly associated with poor survival and early recurrence due to metastasis and regulates the oncogene that is most significantly activated in multiple cancers, including lung cancer. Therefore, our proposal covers the following Areas of Emphasis: (1) understand the molecular mechanisms of initiation and progression to lung cancer by identifying novel oncogene PEA15 and uncovering molecular mechanism of PEA15-mediated regulation of the oncogene and (2) identify innovative strategies for treatment of lung cancer by identifying PEA15 as potential therapeutic target. In our analysis identifying significantly amplified genes in all cancers, we found that PEA15 is highly amplified throughout many cancers, including lung cancer. Its amplification is significantly associated with its mRNA expression and patient survival. Further analysis showed that it regulates the oncogenes that are frequently activated in lung cancer. Therefore, we hypothesize that PEA15 promotes tumor development by activating the oncogene in lung cancer. We will test the hypothesis by using several complementary experimental approaches in cellular and mouse models. Our near-term goals are to determine the molecular mechanisms of a PEA15 in regulation of the oncogene in lung cancer and to examine the therapeutic efficacy of targeting the oncogene. If successful, this work will yield insights about the mechanisms of PEA15-mediated oncogenesis in lung cancer that can be translated into novel treatments for lung cancer patients. Our long-term goal is to establish a novel treatment option for these patients within 5 years after completing the proposed study.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310033
Entities
People
- Ju-Seog Lee
Organizations
- The University of Texas MD Anderson Cancer Center
- United States Army