Innovate to elevate pancreatic cancer care: Immunity leading the way in precision medicine

Research output: Types of ThesisDoctoral ThesisInternal

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Abstract

Pancreatic cancer is an aggressive malignancy with the lowest 5-year survival rate within the field of oncology, ranking third as a cause of cancer-related death in the United States and Europe. Despite years of dedicated research into treatments for pancreatic cancer, improvements in survival rates have been marginal due to multiple challenges. The foremost factor compromising treatment efficacy is the pancreatic tumor microenvironment (TME), distinguished by its complexity, immunosuppressive nature, and patient heterogeneity. This thesis presents the results of studies aimed at unraveling the immunological landscape of pancreatic cancer and exploring avenues to guide personalized treatment options.

Part I of this thesis contains four chapters delving into the immunological and molecular factors impacting the prognosis of patients with resected pancreatic cancer. The goal was to offer valuable insights facilitating the development of tailored and effective immune-based therapies, ultimately elevating patient survival. Part II of this thesis contains five chapters addressing the complexities associated with FOLFIRINOX chemotherapy, a therapeutic pillar in pancreatic cancer. The dilemma surrounding FOLFIRINOX arises due to its toxic nature affecting roughly 70% of patients, coupled with the absence of clinical benefits in 25% of cases. The goal was to examine the multifaced considerations when defining the value of FOLFIRINOX, establish predictive biomarkers for FOLFIRINOX response, and explore the potential synergy of combining immunotherapy with FOLFIRINOX to improve efficacy. Part III of this thesis contains two chapters focusing on rintatolimod, an immune-boosting drug which activates the toll-like receptor 3 (TLR-3), as a potential treatment for advanced pancreatic cancer patients. The goal was to investigate the direct effect of rintatolimod on tumorigenesis in pancreatic cancer cells and, subsequently, the impact of rintatolimod on the peripheral immune landscape.
Original languageEnglish
Awarding Institution
  • Erasmus University Rotterdam
Supervisors/Advisors
  • Aerts, Joachim, Supervisor
  • Malats, Núria, Co-supervisor, External person
  • Mustafa, Dana, Co-supervisor
Award date30 Apr 2024
Place of PublicationRotterdam
Print ISBNs978-94-6483-819-0
Publication statusPublished - 30 Apr 2024

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