Cure of Breast Cancer-Year 6: Novel Approaches in the Therapy of Metastatic Breast Cancer Using Clinical Databases and 3D Organoid Model
ISEF · 2023 Translational Medical Science
Overview
Among various subtypes of breast cancer, triple-negative breast cancer (TNBC) is well-known as aggressive cancer with frequent anticancer drug-resistance and easy metastasis. Nevertheless, the development of new drugs and functional studies for inhibiting the invasiveness of anticancer drug-resistant TNBC are still lacking. Here, we found that the metastatic ability of drug-resistant TNBCs was caused by an increase in inflammatory-mediated Programmed Death Ligand 1 (PD-L1/CD274). PD-L1/CD274 gene had a positive correlation with metastasis-mediated inflammation-related genes, Cell Division Cycle 20 (CDC20), Ubiquitin Specific Peptidase 1 (USP1), TNF Alpha Induced Protein 3 (TNFAIP3), and Caspase 1 (CASP1), which we previously identified, in only the TNBC subtype through the Breast Cancer Gene Expression Miner database containing 4,421 TNBC patient samples. PD-L1 resulted in high invasiveness of taxol- and cisplatin-resistant MDA-MB-231 and BT-549 TNBC cell lines. However, this cancer metastasis by PD-L1 was reduced by the inhibition of inflammation-related genes, CASP1 and CDC20. The exosome inhibitor, GW4869, also significantly reduced cancer cell invasion of chemotherapy-resistant TNBC, and interestingly, a decrease in PD-L1 expression was also observed in this result. Under the three-dimensional (3D) organoid model, we first found metastatic actin fibers on the cancer spheroid surface in the taxol- and cisplatin-resistant TNBC which were strongly prevented by the inflammation inhibitors (Necrostatin-1 and Necrosulfonamide) and exosome inhibitors (Manumycin A and GW4869). These results suggest that inflammation and exosome inhibitors might be novel strategies as anticancer drugs to treat chemoresistant TNBC patients by negatively regulating PD-L1 expression.
Competition history
- ISEF 2023
Resources
Related projects
ISEF · 2020
Cure of Breast Cancer Stage III: Discovering Inflammation Inhibitors as a Novel Approach to Treatment of Triple Negative Breast Cancer Using 3-D Organoid Culture
ISEF · 2022
Cure of Breast Cancer - Year 5: A Novel Approach to Treating Hormonal Breast Cancer Using Diabetic Medication Through Clinical Database and 3D ex vivo Model
ISEF · 2021
Cure of Breast Cancer, Year 4: First Discovery of Target Therapy for Aggressive Hormonal Breast Cancer using Clinical Database and 3D Model
ISEF · 2025
Single-Cell Analysis Based Identification of Unique Markers and Metastasis Mechanism in Triple-Negative Breast Cancer
Closest projects by meaning, across every fair and year in the corpus.
Source: Regeneron International Science and Engineering Fair