Research Projects

Cancer stem cells (CSCs) are a critical subpopulation of tumor cells with self-renewal capacity, quiescence, and resistance to conventional therapies, driving tumor relapse, metastasis, and therapeutic failure. Current treatments focus on bulk tumor populations, leaving CSCs largely untargeted. Recent advancements in 3D organoid cultures derived from primary tumors provide an innovative platform for studying CSC behavior and evaluating therapeutic strategies. Unlike traditional 2D cultures, 3D organoids replicate the tumor microenvironment, enabling clinically relevant drug screening. Drug repurposing of FDA-approved non-steroidal anti-inflammatory drugs (NSAIDs) offers a cost-effective and time-efficient alternative to conventional drug discovery. Preliminary studies in our laboratory have identified significant anticancer activity of specific NSAIDs against breast cancer cell lines, suggesting their potential as CSC-targeted therapies. However, these effects require validation in advanced models that mimic in vivo tumor conditions and investigation into the underlying mechanisms, particularly CSC-specific pathways such as Wnt, Hedgehog, and Notch signalling. Hypothesis: FDA-approved NSAIDs exert anticancer effects by modulating CSC-specific signaling pathways and cytoskeletal dynamics, reducing CSC viability, self-renewal, and invasion. Scientific Objectives: 1. Develop and characterize 3D organoid models from CSCs isolated from primary tumors. 2. Screen FDA-approved NSAIDs for their anticancer effects using CSC-derived 3D organoids. 3. Investigate the mechanisms of action of effective NSAIDs, focusing on CSC-specific pathways and cytoskeletal alterations. 4. Validate the therapeutic potential of identified NSAIDs through functional assays and molecular analyses. Main Experiments: • CSC Isolation and Organoid Development: CSCs will be isolated from primary tumor samples using flow cytometry-based sorting targeting markers like CD44 and CD133. These CSCs will be cultured and characterized. • High-Throughput Drug Screening: A library of FDA-approved NSAIDs will be screened for their effects on organoid viability and proliferation. Promising candidates will be selected based on significant inhibition of CSC growth. • Mechanistic Studies: Molecular techniques, including transcriptomics, proteomics, and metabolomics, will be used to investigate how the identified NSAIDs influence CSC signaling pathways and cytoskeletal dynamics. • Advanced Imaging Significance: This research addresses a major gap in cancer treatment by targeting CSCs, the root cause of drug resistance and tumor recurrence. By repurposing FDA-approved NSAIDs, the project accelerates the identification of cost-effective and personalized cancer therapies. If successful, the findings will significantly enhance the understanding of CSC biology and provide a pathway for rapid clinical translation of new CSC-targeted treatments, ultimately improving patient outcomes and survival.