CeNT seminar (21.02.2025): Targeting mechanisms of pancreatic cancer resistance against therapy: specific role of tumor microenvironment
17 02 2025
Category: CeNT seminars, Main page
The Centre of New Technologies, University of Warsaw invites to a seminar by:
Dr Monika Jakubowska
Malopolska Centre of Biotechnology, Jagiellonian University in Krakow, Poland
Title: Targeting mechanisms of pancreatic cancer resistance against therapy: specific role of tumor microenvironment
Date: February 21st, 2025, Friday
Time: 12:00 pm (Central European Time)
Host: Professor Joanna Trylska, dr Monika Wojciechowska
The seminar will be in the CeNT aula hall (00.142) on the main floor.
Abstract:
Current medical predictions report pancreatic cancer to become the second cause of cancer-related deaths by 2030, mainly because of a lack of effective treatment. Although the strategies of (in)direct targeting a genetic driver of pancreatic cancer development, a mutant KRAS gene, have proven futile, other therapeutic approaches of multi-drug intervention against this form of cancer have entered the clinic. However, these strategies use combinations of cytostatic drugs that mainly target cancerous pancreatic epithelia. Targeting cancer-associated fibroblasts, which in solid pancreatic tumors extensively produce acellular stroma of a hydrogel-like matrix and protein fibers, remains an unmet clinical need. So far, studies of other diseases characterized by strong fibrosis, such as scleroderma, have shown that fibroblasts may evade pro-apoptotic stress signals by changing the balance of BCL-2 family proteins. Under normal conditions, BCL-2 family proteins sensitize the cell to death signals, inducing apoptosis. However, by changing the cellular repertoire of BCL-2 family proteins to overexpress apoptosis inhibitors, cells acquire resistance to stress and evade apoptosis. Surprisingly, a similar pattern of the BCL-2 expression characterizes deadly blood cancers: leukemias and lymphomas. In 2016 small molecule drug, a BCL-2 inhibitor Venetoclax was approved for clinical use against blood cancer. This has inspired our group to test BCL-2 inhibitors in a therapeutic combination with a cytostatic drug, using pre-clinical models of pancreatic cancer that differ in the content of the fibrotic matrix in a tumor.