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Molecular Pathology: Sven Rottenberg

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Sven Rottenberg, DVM, Ph.D.Group leader

About Sven Rottenberg

Cancer Therapy Resistance

Research interest

Patients with tumors 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 tumors eventually emerges, which minimizes therapeutic options and greatly reduces survival. The molecular mechanisms underlying this therapy escape are mostly unclear.

In my group we are studying 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 tumors that arise lack HR-directed DNA repair; an Achilles heel that has provided a therapeutic opportunity to eradicate tumors with DNA damage-causing agents. However, similar to the situation in cancer patients, we observe that cancer cells in these models can escape the deadly effects of classical chemotherapy, novel targeted drugs or radiotherapy. Thus, these resistance models that we have established provide a unique opportunity to explore therapy escape mechanisms.

Sven Rottenberg is currently working at the University of Bern in Switzerland. http://www.vetsuisse.unibe.ch/itpa/content/research/therapy_escape_of_cancer/index_ger.html

Part of his group is still positioned at The Netherlands Cancer Institute.

Co-workers

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Marco Barazas

Ph.D. Student

Experience

"It is my goal to get a better understanding of the impact of inter- or intra-tumor heterogeneity on cancer therapy by studying genetically engineered mouse models for breast cancer. We found that escape mechanisms to classic chemotherapy or radiotherapy not only differ between individual tumors, but also between tumors derived from a unique donor tumor. Using next generation sequencing, proteomics and functional genetic screens, I focus on the question how these tumors have evolved upon therapy exposure and which escape mechanisms have been selected out. My hope is that this knowledge may be useful to improve cancer treatment."

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Duarte, Alexandra

Alexandra Duarte, Ph.D.

Technician

Experience

I completed my undergraduate studies in Cell and Molecular Biology in 2006 (New University of Lisbon, Portugal). I worked for a year at the Instituto Gulbenkian de Ciencia after which I pursued a PhD in David Mann's group at Imperial College London where I studied the DNA damage response in cancer. Having obtained my degree in 2012, I worked for a year as a postdoctoral researcher in the same institution. In 2013 I joined the laboratory of Sven Rottenberg at the NKI as a research technician. I am involved in different projects looking at drug resistance in BRCA1/2-related breast cancer models.

 

 

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Ewa Gogola

Ph.D. Student

Experience

Since August 2012 I'm working in the group of Sven Rottenberg where I aim to determine novel mechanisms of resistance to PARP inhibition in tumors deficient in homologous recombination. In my project I combine functional in vitro screens with in vivo approaches using our genetically engineered mouse models that closely resemble Brca1/2-related breast cancer.

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Key publications View All Publications

  • REV7 counteracts DNA double-strand break resection and affects PARP inhibition

    (2015) Nature. May 28;521(7553):541-4. doi: 10.1038/nature14328. Epub 2015 Mar 23.

    Xu G, Chapman JR, Brandsma I, Yuan J, Mistrik M, Bouwman P, Bartkova J, Gogola E, Warmerdam D, Barazas M, Jaspers JE, Watanabe K, Pieterse et al.

    Link to PubMed
  • Loss of 53BP1 causes PARP inhibitor resistance in Brca1-mutated mouse mammary tumors

    (2013) Cancer Discov. 2013 Jan;3(1):68-81. doi: 10.1158/2159-8290.CD-12-0049. Epub 2012 Oct 25

    Jaspers JE, Kersbergen A, Boon U, Sol W, van Deemter L, Zander SA, Drost R, Wientjens E, Ji J, Aly A, Doroshow JH, Cranston A, Martin NM, et al.

    Link to PubMed
 
 

Recent publications View All Publications

  • Progression through mitosis promotes PARP inhibitor-induced cytotoxicity in homologous recombination-deficient cancer cells

    (2017) Nat Commun. Jul 17;8:15981. doi: 10.1038/ncomms15981.

    Schoonen PM, Talens F, Stok C, Gogola E, Heijink AM, Bouwman P, Foijer F, Tarsounas M, Blatter S, Jonkers J, Rottenberg S, van Vugt MATM. ...

    Link to PubMed
  • Progression through mitosis promotes PARP inhibitor-induced cytotoxicity in homologous recombination-deficient cancer cells

    (2017) Nat Commun. Jul 17;8:15981. doi: 10.1038/ncomms15981

    Schoonen PM, Talens F, Stok C, Gogola E, Heijink AM, Bouwman P, Foijer F, Tarsounas M, Blatter S, Jonkers J, Rottenberg S, van Vugt ...

    Link to PubMed
 

Contact

  • Office manager

    Suzanne Romijn

  • E-mail

    s.romijn@nki.nl

  • Telephone Number

    +31 20 512 9168

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