Blueprints of disease: precision platforms for modelling breast cancer

Author(s):
Lutz, C. (0009-0002-5152-6785)
Published
2026
Publication type
Doctoral Thesis

Abstract

Breast cancer (BC) is a clinically and biologically heterogeneous disease. Luminal BC, the most prevalent subtype, is characterised by its dependence on hormones and presents ongoing challenges for treatment stratification and mechanistic understanding, in large part due to the lack of clinically relevant models. The overarching aim of this thesis is to develop, refine, and apply diverse preclinical modelling platforms to interrogate the drivers of luminal BC progression, heterogeneity, and therapeutic response. By combining in vivo modelling, genomic engineering, and large-scale phenotypic profiling, this work provides novel tools and insights into the functional biology of luminal BC. The thesis is structured around multiple platform modelling strategies, each applying new and refined techniques to address complementary aspects of (luminal) BC modelling and tumour biology.

Breast cancerModellingIn vivo modelsSomatic engineeringHormone receptorOestrogenTreatment resistanceCancer progressionXenograftsBase editing
Defense date
2026-03-10
Language
English
Supervisor(s)
Jonkers, J.M.M.
Advisor(s)
Messal, H.A.
Committee member(s)
Lange, E.C.M. de; Visser, K.E. de; Rheenen, J. van; Martens, J.
Qualification
Ph.D.
Degree granting institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University, Leiden
hdl
1887/4296062
doi
10.60602/1887-4296062
ISBN(s)
9789464965483

Funding

Sponsorship
The research described in this thesis was performed at the division of Molecular Pathology at the Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI-AvL) (Amsterdam, The Netherlands). The research was financially supported by Cancer Research UK, KWF Kankerbestrijding, and Oncode Institute.