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Pharmacology: Olaf van Tellingen

Van Tellingen Liggend

Olaf van Tellingen, Ph.D.Group leader

About Olaf van Tellingen

Olaf van Tellingen

Glioblastoma (GBM) is a uniformly fatal disease. The location and invasive nature of GBM renders complete surgical resection impossible. Although radiotherapy is important for disease management, side effects prohibit the delivery of curative doses. Despite the successful introduction of novel targeted therapeutics in some other solid cancer types, clinical trials in GBM have all failed. The mission of our preclinical research group is to develop and validate more effective pharmacotherapies for this disease. One of the spearheads of our research is aimed at highlighting the important role of the blood-brain barrier (BBB) in treatment failures. Although disruption of the BBB is common, this grossly affects areas of the tumor that can be surgically resected. However, the non-resectable tumor cells that have colonized the surrounding normal brain tissue are protected by the BBB and are the source of the inevitable recurrence. Just a few mainly small hydrophobic drugs display some efficacy against GBM. In particular, drug transporting proteins like ABCB1 (P-gp) and ABCG2 (BCRP) hinder the entry of most of the other effective anticancer agents, including many targeted agents. Thus, in order to develop more successful pharmacotherapy, our research aims to identify potentially useful agents that are no or weak substrates of these drug transporters. Alternatively, we are trying to improve drug penetration into brain tumors by using drug efflux pump inhibitors or carrier systems. 

Other hurdles to effective pharmacotherapies for GBM are the combined activation of multiple oncogenic pathways and intra-tumor heterogeneity. With multiple aberrant signaling pathways driving GBM, single target-single agent pharmacotherapies are likely to fail, even when using drugs that can penetrate the BBB. Consequently, we are exploring combinations of targeted agent that should cause concomitant inhibition of the common glioma associated oncogenic signaling pathways. Moreover, as radiotherapy is the cornerstone of the standard therapy, we are also actively investigating the options of radiosensitization by small molecule drugs. For this we closely collaborate with the research group of Gerben Borst. 

GBM is a highly complex disease that cannot be modelled with high-fidelity using in vitro models only. Consequently, we rely heavily on in vivo models for our research. We have developed and acquired a range of experimental mouse models of GBM that mimic many aspects of GBM in patients very closely. These include genetically engineered mouse models and human and murine transplantable glioma models. With our top-class animal facility housing 7T MRI, image-guided radiotherapy system and molecular and optical imaging modalities, we can make optimal use our state-of the-art models for interrogating the effects of experimental interventions. The impact of the drug transporters in the BBB is being studied by using transporter knockout mouse models. In collaborations with the research group of Jacco van Rheenen we are also implementing intravital imaging as a tool to visualize the response of intracranial tumors to therapies. With the help of these models, we try to uncover potentially exploitable vulnerabilities of gliomas in order to improve the prospects of patients that suffer from this devastating disease.

Co-workers

Ceren Citirikkaya

Ceren Çitirikkaya

Technician

Experience

I started my internship as a graduate student in the lab of dr. Olaf van Tellingen in 2016. My project was mainly focused on obtaining therapeutically active plasma levels in mice. I received my Bachelor of Science degree and animal experimental license from the University of Applied Sciences Leiden in 2017.

After my graduation I joined the Van Tellingen lab as a research technician, working on various in vitro and in vivo projects that aim to develop a better treatment for glioblastoma

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Mark de Gooijer

Ph.D. student

Experience

As a PhD student in the lab of dr. Olaf van Tellingen, my research mainly focuses on the treatment of brain tumors and overcoming the challenge that the blood-brain barrier poses to the development of effective therapies.

Prior to joining the Division of Pharmacology at the NKI, I received training as a student in the labs of prof. Thomas Wurdinger at the Cancer Center Amsterdam (CCA) and dr. Bakhos Tannous at Massachusetts General Hospital, Boston, whilst obtaining my Master of Science degree in Oncology from VU university in Amsterdam.

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Çolakoğlu, Hilâl

Hilal Çolakoğlu

Technician

Experience

I joined the Van Tellingen lab in November 2017 as a bachelor student from the Biology and Medical Laboratory Research program at the University of Rotterdam of Applied Sciences. My main focus was studying the efficacy of motor protein inhibitors against glioblastoma. After obtaining my Bachelor of Science degree in July 2018, I have continued working in the Van Tellingen lab as a technician, mainly focusing on developing new treatment strategies for glioblastoma.

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Research updates View All Updates

  • Grant Stichting Stophersentumoren

    We have received a research grant from the Stichting Stophersentumoren, which is being used to for a preclinical proof-of-concept study to assess whether we can improve the therapy of glioblastoma by inhibition of glioma invasion.

  • Grant Stichting Aniek Hendriksz Second to None

    We have received a grant of Stichting Aniek Hendriksz Second to None, which is being used to design and test the use of therapies with clever combinations f targeted agent.

Key publications View All Publications

  • Identification of a druggable pathway controlling glioblastoma invasiveness.

    Cell Rep. 2017;20(1):48-60

    Pencheva N, De Gooijer MC, Vis DJ, Wessels LFA, Wurdinger T, Van Tellingen O, Bernards R.

    Link to PubMed
  • Overcoming the blood-brain tumor barrier for effective glioblastoma treatment

    Drug Resist Updat. 2015;19:1-12

    Van Tellingen O, Arik-Yetkin B, De Gooijer MC, Wesseling P, Wurdinger T, De Vries EH.

    Link to PubMed
 
 

Recent publications View All Publications

  • Improved brain penetration and antitumor efficacy of temozolomide by inhibition of ABCB1 and ABCG2

    Neoplasia, 2018;20(7):210-220.

    De Gooijer MC, De Vries NA, Buckle T, Buil LCM, Beijnen JH, Boogerd W, Van Tellingen O.

    Link to PubMed
  • The impact of P-glycoprotein and Breast Cancer Resistance Protein on the brain pharmacokinetics and pharmacodynamics of a panel of MEK inhibitors

    Int J Cancer 2018;142(2);381-91.

    De Gooijer MC, Zhang P, Weijer R, Buil LCM, Beijnen JH, Van Tellingen O.

    Link to PubMed
 

Contact

  • Office manager

    Thea Eggenhuizen

  • E-mail

    t.eggenhuizen_at_nki.nl

  • Telephone Number

    020-5122035

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