Chromosomal instability (CIN) is a hallmark feature that discriminates cancer cells from normal cells. We investigate the biology of chromosomal instable cells to discover vulnerabilities specific to CIN cells that can be exploited in cancer therapy.

Chromosomal instability (CIN) is a hallmark feature of cancer. CIN leads to cells with an abnormal DNA content, a state known as aneuploidy affecting >80% of all cancers. Paradoxically, in untransformed cells, CIN and aneuploidy decrease cellular fitness and lead to activation of stress pathways. This suggests that cancer cells have found ways to cope with the downsides of CIN. A better understanding of these coping strategies can lead to new therapies that target these mechanisms, and thus selectively kill the aneuploid cancer cells with fewer side effects on healthy cells.

In the Foijer lab, we study how cells deal with CIN and the resulting aneuploidy, in vitro as well as in vivo, to better understand what discriminates an aneuploid (cancer) cell from a normal cell. Importantly, we exploit our findings to design new strategies that selectively target aneuploid cells and collaborate with clinicians to translate our findings into clinical practice. The work in the lab focusses on four main themes: 1) Development of technology and in vivo models to faithfully model and quantify CIN and aneuploidy 2) Understanding how karyotype evolution shapes the genome landscape of cancer 3) Studies of the molecular mechanisms that discriminate aneuploid (cancer) cells from normal cells 4) Efforts to exploit our mechanistic findings to design therapies that selectively kill cancer cells with a CIN phenotype


What has our research yielded so far?

Over the past years, we have developed several models to study CIN. We now use these to understand how CIN leads to cancer and other pathologies to find better ways to treat cancers with a CIN phenotype. Importantly, our work has led to new technologies to better quantify CIN in primary tumors, to improved models to study the consequences of CIN and to compounds that can be used to eradicate cells displaying CIN.

  • Chromosomal instability will not only lead to aneuploid cells, but also to differences in chromosome copy numbers between the individual cancer cells. The latter is a concept known as intratumour heterogeneity and is associated with a poor prognosis when observed in cancer. While many platforms can faithfully quantify aneuploidy, it has been much harder to quantify intratumour karyotype heterogeneity. We therefore, together with the lab of Peter Lansdorp, developed a platform that can measure the DNA content of induvial (cancer) cells using shallow whole genome sequencing. We now frequently use this platform with many (inter)national collaborators to better understand how CIN drives tumour (cell) evolution. We expect that our constantly-improving toolbox will improve cancer diagnosis in the near future as well.

  • Chromosomal instability and the resulting aneuploidy are detrimental to non-cancer cells. However, more than 80% of all cancers are aneuploid, suggesting that cancer cells have found ways to cope with the consequences of CIN. Therefore, interfering with these coping mechanisms could be a powerful way to treat aneuploid cancers. While finding such CIN-related intervention strategies is very much ongoing in the lab, we recently discovered that cells with a CIN phenotype are much more sensitive to inhibition of a kinase, Src kinase, compared to cells that do not display CIN. We find that Src inhibition acts synergistically with established anti-cancer drugs that provoke CIN. Therefore, our findings could be a first step towards combination therapy of Src inhibition with established anti-cancer drugs.


Floris Foijer
Floris Foijer Associate professor, Group Leader of the Laboratory of Genomic Instability in Development and Disease

University Medical Center Groningen (UMCG)
European Research Institute for the Biology of Ageing (ERIBA)
PO Box 196, Internal Zip Code FA50
9700 AD Groningen
The Netherlands

Visiting address
University Medical Center Groningen (UMCG)
European Research Institute for the Biology of Ageing (ERIBA)
Antonius Deusinglaan 1, building 3226
9713 AV Groningen