Research Geert Roeyen

Abstract

Our team proposes an innovative project that integrates a 3D patient-derived pancreatic microtumor model with multiomics analyses to dissect molecular mechanisms of Pancreatic Ductal Adenocarcinoma (PDAC) at a single-cell, patient-specific level. A key strength of our approach is the direct link between the clinic and the laboratory, facilitated by the surgeon's unique position. This connection is crucial for accurately recreating the patient's tumor in the lab, allowing us to obtain high-quality, fresh tumor samples directly from surgeries. We aim to understand the intercommunication and reprogramming between malignant cells, stromal cells, and macrophages by applying single-cell RNA-sequencing, secretomics, and proteomics. Additionally, we will employ our AI-driven high-throughput drug screening platform to visualize live cell interactions and study cell behavior in a 3D context. This setup allows us to scrutinize the biological and therapeutic impact of identified communication pathways by testing new therapeutic strategies on our microtumor model, thereby monitoring cell-specific responses. This research could revolutionize our understanding of PDAC, paving the way for the identification of new therapeutic targets and the development of effective treatments. The synergy between the clinic

Researcher(s)

• Promoter: Roeyen Geert
• Fellow: Roeyen Geert

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Pancreatic cancer is one of the most lethal cancer types worldwide, with barely a quarter of the patients still alive one year after diagnosis and a 5-year overall survival below 10%. This dismal outcome is mainly due to its high resistance to all current therapies. Therefore, innovative and effective treatment options are urgently needed for these patients. The tumor microenvironment is stated as the major confounding factor involved in therapy failure. This tumor microenvironment acts as a dense fibrotic shield around the pancreatic cancer cells and additionally creates an immune suppressive environment. Therefore, combination therapies that target both cancer cells and modulate this immune suppressive tumor microenvironment are the next-generation strategies. Hence, in this project I will first modulate the fibrotic shield by using ormeloxifene. This compound is included in the list for drug repurposing in oncology, underlining the fastest and most cost-effective way towards clinical application. Subsequently, I will reinforce the patient's own immune system to eliminate pancreatic cancer cells by exploiting next-generation inhibitory immune checkpoints. With this rationally designed combination, I aim to provide a solid, scientific rationale to initiate a novel clinical trial for pancreatic cancer patients who are in dire need for new treatments options.

Researcher(s)

• Promoter: Smits Evelien
• Co-promoter: Peeters Marc
• Co-promoter: Roeyen Geert
• Fellow: Quatannens Delphine

Research team(s)

• Center for Oncological Research (CORE)

Project type(s)

• Research Project