All India Institute Of Medical Sciences, New Delhi
pramodgautam_13@yahoo.com
Project Overview
Pancreatic cancer is one of the most aggressive and lethal gastrointestinal cancers, with a dismal 5-year survival rate of only 5-8%. A key feature of pancreatic cancer is the dense tumor stroma, which fosters a tumor-promoting microenvironment. Inflammatory processes within the tumor recruit various immune cells, such as macrophages, NK cells, B cells, T cells, and γδ T cells. These immune cells can differentiate into either tumor-suppressing or tumor-promoting phenotypes depending on the tumor microenvironment (TME). While some components of the TME may enhance immune responses, others can obstruct immune cell function, leading to immune evasion. Extracellular vesicles, especially exosomes produced by cancer cells, play a major role in this immune escape by carrying miRNAs that impair immune cell activation, survival, and function. Despite the growing recognition of miRNAs as critical regulators in cancer progression, their full potential in modulating tumor immunity and therapeutic responses in pancreatic cancer remains largely unexplored. (Novelty) Several reports document various miRNA therapy targets for lymphoma, liver cancer, neuroblastoma, colorectal cancer and lung cancer along with other disorders such as periphery artery disease and myocardial infraction being tested in pre-clinical trials but only few studies have identified such targets for Pancreatic cancer. This study is novel in its focus on identifying specific miRNA targets for PDAC, offering a potentially more effective alternative to traditional chemotherapy and radiation treatments. The research will explore miRNAs' role in regulating immune cell behavior and tumor progression within the pancreatic TME, opening new avenues for targeted therapeutic strategies. (Objectives) The primary objective of this study is to identify miRNA-based therapeutic targets for PDAC, focusing on their potential to modulate tumor progression and immune evasion. The research aims to uncover the role of miRNAs in the tumor microenvironment and immune modulation in PDAC. (Methods) The study will utilize molecular biology techniques to isolate and analyze exosomal miRNAs from PDAC cell lines and patient samples. Bioinformatics tools will be employed to identify miRNAs involved in tumorigenesis, immune cell modulation, and metastasis. Functional assays will be conducted to assess the impact of miRNA manipulation on tumor progression and immune cell responses. (Expected Outcome) This research is expected to identify novel miRNA targets that could serve as potential therapeutic agents for PDAC. The findings may lead to the development of miRNA-based treatments, offering a more effective alternative to traditional chemotherapy and radiation, and providing insights into how miRNAs can modulate the immune microenvironment in pancreatic cancer.