A Novel Role of Caveolin-2 in Human Non-Small Cell Lung Cancer Progression and Angiogenesis in Vitro and in Vivo
Abstract
Scientific Objective and Rationale: The proposed research will help us understand the role of the membrane protein caveolin-2 (Cav-2) in the progression of clinically significant non-small cell lung cancer (NSCLC), in particular, lung adenocarcinoma (AC), the most common type of lung cancer. Lung cancer is the leading cause of cancer-related death worldwide. In the United States, the disease accounts for more deaths than the next four major cancers combined, and almost 450 people will die of cancer of the lung every day. This devastating disease disproportionately affects military Veterans, and within this group, lung cancer incidence is not only higher than the civilian population but also survival rates are lower. Unfortunately, current therapies are ineffective, since approximately 74% of lung cancer patients die within 5 years of diagnosis. NSCLC represents about 80% of all lung cancers, while the remaining 20% are small cell lung carcinomas (SCLC). AC of the lung is the most common subtype of NSCLC. Since the prognosis for patients with NSCLC, especially with lung AC, is poor, identification of new therapeutic targets is urgently needed. The membrane protein Cav-2 was originally discovered as a component of plasma membrane caveolae and lipid rafts, but is also found in other subcellular compartments where it may have different functional roles. Clinical studies show a strong correlation between Cav-2 protein positivity and mortality rate of patients with lung AC, suggesting that Cav-2 might play a positive role in lung AC progression. However, the direct experimental evidence supporting the positive role for Cav-2 in lung AC progression is absent. Ultimate Applicability of the Research: A positive outcome of this research will establish the basis for more detailed studies aimed at determining the precise molecular mechanisms underlying stimulation and progression of human NSCLC, especially AC of the lung by Cav-2. In addition, a successful outcome of this study will potentially lead to development of novel therapeutic approaches targeting Cav-2 either alone or in combination with existing treatments in patients with NSCLC and in particular with AC of the lung, to combat the progression of lung cancer. Due to primarily basic nature of this research in its current stage, it is estimated (to the best of our ability) that it may take at least 5 years to achieve clinically relevant outcome. Likely Contributions of this Study to Advancing the Field of Lung Cancer Research and/or Patient Care: This research will likely advance the field of lung cancer via contributing to better understanding the molecular mechanisms that lead to various subtypes of lung cancer. In addition, these studies will likely help identify innovative strategies for prevention and treatment of early and/or localized lung cancer via identifying Cav-2 as a novel target for therapeutic strategies treating patients with NSCLC, especially patients with AC of the lung.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510624
Entities
People
- Grzegorz Sowa
Organizations
- United States Army
- University of Missouri