Pancreatic ductal adenocarcinoma (PDAC) is a powerful rival in the cancer field, known for its invisible progress and devastating effects. It is one of the leading causes of cancer-related deaths worldwide and is expected to be the main cause in the next decade. The killing nature of PDAC lies in its aggressiveness, deep anatomical position of the pancreas, frequent diagnosis at the advanced stage, and the notorious reputation of shrugging and shrugging. This terrible situation underscores an emergency action calling on the scientific community to explain the molecular mysteries that drive PDAC ruthlessly, paving the way for innovative and effective therapeutic interventions.
Known for its aggressive and challenging therapeutic landscape, PDAC will soon face new competitors in the battle against cancer progress. Professor Outender Manne and colleagues worked with researchers at the University of Washington at the University of Alabama and the University of Texas Rio Grande Valley, A groundbreaking study published in the journal Peer Review Tumor. The results elucidate a novel therapeutic target, Trip13. This protein is overexpressed in PDAC tumors and plays an important role in tumor growth, metastasis, and chemotherapy resistance.
The innovative approach of this study focused on the genetic knockdown of Trip13 and its pharmacological inhibitory effect using the small molecule inhibitor DCZ0415. Professor Manne and his colleagues carefully documented the substantial effect of Trip13 inhibition on the proliferation, invasion, migration and metastasis of PDAC cells. Key signaling pathways associated with cancer progression are disrupted, marking an important step in PDAC treatment strategies.
The basis of this extraordinary study depends on a diverse, powerful methodological framework. Initially, the research team tried to understand the oncogenic effects of TRIP13 in PDAC. They found that Trip13 acts as a promoter for PDAC growth and transfer. It is worth noting that the inhibitor DCZ0415 alone targeted TRIP13 and targeted with standard treatments effectively stopped the progress of PDAC characterized by high TRIP13 expression.
To explore this role within the scope of PDAC cell behavior, the team adopted a variety of human PDAC cell lines, demonstrating a range of genetic backgrounds. “We procured human PDAC cell lines that exhibited various mutational states. These lines played a role in our comprehensive analysis,” explains Professor Manne.
A key aspect of this study is the assessment of the migration potential of PDAC cells through wound healing assays. This approach not only elucidates the effect of Trip13 inhibition on cell migration, but also provides a tangible measure of inhibitor efficacy. “For the ShRNA study, wound healing assays were performed for TRIP13 hair removal and control cells as well as DCZ0415-treated cells to determine the effect on migration. This approach allows us to visually and quantitatively evaluate the effects of Trip13-targeted PDAC cell dynamics.
The implications of these findings are profound, provide justification for biomarker-driven clinical trials and offer hope for improving therapeutic strategies for PDAC. By targeting TRIP13, the study not only paves the way for potentially effective treatments, but also makes a significant contribution to our understanding of the molecular basis of this deadly disease. All in all, the innovative research of Professor Manne and his team marks a significant step forward in the fight against PDAC. Through a meticulous methodology and focusing on the role of Trip13 in the progression of PDAC, this study opens new avenues for therapeutic interventions, bringing hope to patients facing this challenging diagnosis.
Journal Reference
Farrukh Afaq, Sumit Agarwal, Prachi Bajpai et al., “Targeting oncogenic AAA-ATPase Trip13 reduces progression of pancreatic ductal adenocarcinoma,” Neoplasia, 2024.
doi: https://doi.org/10.1016/j.neo.2023.100951.
About the Author
Mis. Dr. Manne is a professor of pathology, surgery, and epidemiology at the University of Birmingham (UAB). He is also the director of the discipline of translational anatomical pathology, co-director of UAB tissue biosector, senior scientist at O’Neal Comprehensive Cancer Center, senior scientist at the Center for Nutrition and Obesity Research, and a senior scientist and a minority at the UAB Heersink School of Medicine Center for Health and Health Equity Research. For about three decades, Professor Manne has served as an R, P and U series grant initiated by researchers at the National Institutes of Health/National Cancer Institute (NCI). He has published widely in the field of cancer molecular biomarkers discovery and validation and cancer health differences in several human malignant tumors. He has developed several preclinical cancer (patient-derived xenografts and organs) models for experimental drug testing. Other aspects of Professor Manne’s academic career are training students, physicians, and scientists to conduct cancer research and pursue productive academic careers.
