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Taking on cancer therapy resistance

The group of Professor Sven Rottenberg at the Institute of Animal Pathology, University of Bern, Switzerland, aims at understanding the basic mechanisms that cause cancer therapy escape

Their research is carried out in collaboration with various other international groups, particularly with the group of Jos Jonkers at the Netherlands Cancer Institute (NKI) in the Dutch capital Amsterdam.

Rottenberg has been working at the University of Bern since August 2014, closely alongside the NKI. His research is supported by the Swiss National Science Foundation, the Swiss Cancer League and the Dutch Cancer League (KWF). In 2016, Rottenberg received support from the European Research Council (ERC) for researching cancer therapy resistance with a consolidator grant (‘SYNVIA’).

Patients with tumours that are defective in DNA repair by homologous recombination (HR) are often sensitive to DNA-repair targeting agents. However, despite initial responses to cancer therapy, resistance of primary or disseminated tumours eventually emerges, which minimises therapeutic options and greatly reduces survival. The molecular mechanisms underlying this therapy escape are mostly unclear.

cancer therapy

Cancer therapy escape studies

The group studies the basic mechanisms of therapy escape by using distinguished mouse models for BRCA1- or BRCA2-deficient breast cancer, which closely mimic the disease found in humans. Due to the BRCA inactivation, the tumours that arise lack HR-directed DNA repair – an Achilles heel that has provided a therapeutic opportunity to eradicate tumours with DNA damage-causing agents.

However, like the situation in cancer patients, the group observes that cancer cells in these models can escape the deadly effects of classical chemotherapy, novel targeted drugs or radiotherapy. Thus, these resistance models established by the group provide a unique opportunity to explore therapy escape mechanisms.

The group’s mission is to provide outstanding research to support clinicians understanding the molecular basis of cancer therapy resistance. Moreover, the home institution has established a comparative pathology platform (COMPATH) to support translation research involving animal models of human diseases. What makes this platform different is the multidisciplinary team with complimentary know-how in the area of pre-clinical, translational, clinical and basic science. As a University unit, the group also aims to provide excellent training opportunities for undergraduate and postgraduate students in the topic of precision medicine.

Services include gross and microscopic examination of whole animals and organs as well as any biopsies. In regard to biopsies, the group also provides an exceptional high standard for the interpretation of skin biopsies.

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  • Therapy escape of cancer;
  • Host-pathogen interactions;
  • Applied dermatopathology;
  • Comparative Pathology (COMPATH).
  • 2018 – 2022 Swiss Cancer League (KLS-4282-08-2017) Understanding the role of the CST complex in the synthetic lethal interaction between BRCA1 deficiency and PARP inhibition;
  • 2016 – 2021 European Research Council (ERC) consolidator grant (681572): Synthetic viability of homologous recombination-deficient cancers (SYNVIA);
  • 2015 – 2018 SNSF grant (310030_156869): Mechanisms of PARP inhibitor resistance of BRCA2-deficient mouse mammary tumours.

Inspired Front Cover in Health Europa Quarterly – Issue 4
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