Research Theme 4

Causes and consequences of genetic instability.


Genetic instability is a major driver of tumour development and progression. It is an important factor in therapy response and relapse during all relevant stages of carcinogenesis and in every aspect of treatment. It causes genetic heterogeneity in cell populations, which creates a process of rapid evolution in which neighbouring cells can outcompete each other during growth or treatment. Better understanding of the underlying mechanisms may allow us to exploit the genetic instability to improve therapy.

Theme aims

  1. Find molecular mechanisms that protect genome stability – Using state-of-the-art molecular and cellular approaches we aim to study how cells respond to genomic damage. This can lead to better understanding of mechanisms of DNA repair and regulation of cell division.
  2. Examine mechanisms of genome instability – Using patient-derived samples and model systems we will study which forms of genetic instability exist in which cancers. We aim to identify the underlying genetic and environmental causes of this genetic instability.
  3. Study genome instability in cancer development and progression – We will study the heterogeneity of cancer cells and its links to genome instability. Using single-cell-based technologies on well-defined tumour samples and model systems, we will analyze heterogeneity during cancer initiation, development and progression.
  4. Explore inducing genome instability as cancer therapy – Better understanding of the mechanisms underlying genome instability can be exploited to uncover new druggable targets. We will test how specific pathways leading to genome instability can be targeted.

Please find a more detailed description in our Strategic Plan.

Theme leader

Geert Kops Head of the Institute


Titia Sixma Oncode Investigator
Roland Kanaar

Roland Kanaar

Oncode Investigator

Oncode Investigator

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