The lack of therapeutic response in high-grade tumors is mainly attributed to the acquisition of cancer cells’ resistance to death. However, numerous data show a paradoxical positive correlation between the presence of dying cells in tumor tissue and enhanced tumor growth. When a tumor cell enters the death program, it actively regulates tissue renewal through a pathway called the “Phoenix rising”. The leading role in this route belongs to the pro-inflammatory molecule prostaglandin E2 (PGE2), therefore, its inhibition is crucial in tumor repopulation breakdown. ADVANCED intends to upgrade basic knowledge of the cell death-triggered tumor repopulation in high-grade colorectal cancer, as a prototype of an inflammation-driven tumor, and to explore the therapeutic potential of new anti-inflammatory drugs belonging to inhibitors of cyclooxygenase-2 (COX-2) and lipoxygenases (LOX), as well as hybrid molecules of chemotherapeutic and anti-inflammatory drugs. We strive to develop a new tumor repopulation model through the establishment of mouse-derived organoids (MDOs). The molecular pattern of tumor repopulation will be defined by transcriptional profiling, while selected drugs will be screened starting from the novel MDOs and syngeneic in vivo models, and ending with colorectal cancer patient-derived organoids (PDOs). The results of this project will help the development of strategies for high-grade colorectal cancer treatment by preventing inflammation-driven repopulation.

Period: 2024-2027.

Project Website: https://www.projectadvanced.rs

Project coordinator: Dr. Danijela Maksimović-Ivanić, Institute for Biological Research “Siniša Stanković” – National Institute of the Republic of Serbia, University of Belgrade

Team members from IBISS:
Dr. Sanja Mijatović, Department of Immunology
Dr. Marija Mojić, Department of Immunology
Dr. Jasmina Živanović, Department of Citology
Dr. Nataša Radulović, Department of Immunology
Dr. Tamara Krajnović, Department of Immunology
Sanja Jelača, Department of Immunology
Ekatarina Mihajlović, Department of Immunology
Teodora Komazec, Department of Immunology

External advisors:
Prof. Dr. Duško Dunđerović, Faculty of Medicine, University of Belgrade
Prof. Dr. Andrija Antić, Faculty of Medicine, University of Belgrade
Prof. Dr. Ivan Soldatović, Faculty of Medicine, University of Belgrade
Prof. Dr. Evamarie Hey-Hawkins, Faculty of Chemistry and Mineralogy, Leipzig University
Prof. Dr. Goran Kaluđerović, Department of Engineering and Natural Sciences, University of Applied Sciences Merseburg