We use cookies to enhance your site experience. This website stores data such as cookies to enable essential site functionality, as well as marketing, personalization and analytics. By continuing to use our website, you consent to cookies being used. Review our Privacy Policy for more information.
Daniel Pyo, BS - University of Maryland School of Medicine, Baltimore, MD
D. J. Pyo1, S. Roy2, D. Kunaprayoon2, Z. Keepers1, F. Carrier2, A. Mackerrell3, and H. D. Shukla2; 1University of Maryland School of Medicine, Baltimore, MD, 2Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, 3University of Maryland School of Pharmacy, Baltimore, MD
Purpose/Objective(s):
Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death, often complicated by resistance to radiation therapy (RT). Emerging evidence suggests that dysregulated caveolin-1 (CAV1), a membrane protein that interacts with EGFR, plays a critical role in tumor progression and therapeutic resistance. This study seeks to elucidate the stage specific expression of CAV1 in NSCLC and investigate how CAV1 could be used as a biomarker for RT resistance.
Materials/Methods:
TMA slides from 41 patients with lung squamous cell carcinoma (Stage I: n=20; II: n=13; III: n=8) and matching normal tissue were stained for CAV1. Imaging of TMAs were performed using Leica CS2 Imager and Aperio Image Scope software. A composite score that included the number of CAV1-positive cells and the strength of CAV1 expression was assigned to each slide by an interpreting pathologist. An additional 12 samples (4 per stage) were also acquired from the University of Maryland Medical Center, with IHC staining being conducted to determine expression levels of CAV1 and EGFR in samples across the different NSCLC stages. Imaging was then conducted with ECHO automated microscopy and results were analyzed with pathology consultation.
Results:
IHC staining of 41 clinical samples (stages I, II & III) showed strong over-expression of CAV1 in squamous cell lung cancer tissues when compared to the matching normal controls (p <0.001). CAV1 expression was 25-75% higher in tumor tissues of different stages with increasing composite scores by stage. Furthermore, a larger 185-patient cohort IHC exhibited high CAV1 expression of 44.0% in NSCLC tissues (p<0.0001). We have also shown that CAV1 interacts with EGFR and enhances resistance to therapies. TCGA analysis of patient samples showed that CAV-1 gene amplification was linked to a worse prognosis. Through computer-aided drug design (CADD) we have also identified Landiolol and Vilanterol as small molecule CAV1 inhibitors for therapy.
Conclusion:
CAV1 is significantly overexpressed in NSCLC across all stages and correlates with disease progression. Its interactions with EGFR and genetic amplification are linked to worse outcomes and increased resistance. These results identify CAV1 as a robust prognostic biomarker and a promising therapeutic target for radiosensitization. Future work will further characterize CAV1-EGFR interactions to refine targeted therapies for overcoming treatment resistance.
