PhD defence

Acquired resistance in pancreatic cancer: characterization and exploration of actionable targets of a multifactorial disease

• C. Bergonzini

Date

Tuesday 27 January 2026

Time

14:30 - 15:30 hour

Address

Academy Building
Rapenburg 73
2311 GJ Leiden

Supervisor(s)

• Prof.dr. E. Danen
• Prof.dr. T. Schmidt
• Prof.dr. E. Giovannetti

Summary

Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is one of the deadliest types of cancer. Although it affects fewer people than many other cancers, it is often diagnosed at a late stage, when surgery is no longer an option. As a result, most patients are treated with chemotherapy. Unfortunately, these treatments frequently lose effectiveness because cancer cells rapidly adapt and become resistant. One factor that may contribute to this resistance is the tissue surrounding the tumor, which is unusually dense and stiff. This physical environment can influence how cancer cells behave, but its role in treatment failure is still not fully understood.

This thesis investigates how pancreatic cancer cells develop resistance to chemotherapy and studies the interplay between this process and the physical properties of the tumor environment. Using multiple laboratory models of PDAC that no longer respond to commonly used drugs, we identified shared strategies that cancer cells use to survive treatment. We also found that a specific protein involved in how cells attach to their surroundings (Integrin subunit alpha 2 - ITGA2) increases in stiff tumor environments and is linked to poorer outcomes in patients receiving chemotherapy.

Finally, we observed that drug-resistant cancer cells are display altered mechanical properties, regardless of the drug they became resistant to. Overall, this work shows that both molecular and physical changes help pancreatic cancer escape treatment and highlights new directions for improving future therapies.

PhD dissertations

Approximately one week after the defence, PhD dissertations by Leiden PhD students are available digitally through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.

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