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Pharmacology: Jos Beijnen


Jos BeijnenHead of the Pharmacy

About Pharmacology

Research interest: Personalized Cancer Treatment

Phase I Clinical Trials with targeted therapies
The development of anti-cancer therapies has undergone a radical change over the last decades: from conventional cytotoxic drugs that don't discriminate between normal and tumor cells, to so-called targeted therapies which inhibit a specific target within a tumor cell.
The targets are mostly comprised of receptors or tyrosine kinases that have become aberrant in tumor cells, which can cause uncontrolled cellular signaling and growth.
Within our research group, we perform many phase I studies with inhibitors of these specific targets, both in the form of small-molecule inhibitors as well as monoclonal antibodies. Since this is the first time these anti-cancer therapies are administered to humans, the main goal of these studies is to characterize the safety and pharmacokinetic profile and to determine a recommended dose for further clinical development.
In recent years, it has become apparent that these targeted therapies have relatively modest anti-tumor activity, which is mostly due to the tumor cells developing resistance through mutations in parallel cellular signaling pathways. Thus, development of these compounds has steered more towards combining these compounds.

Pharmacodynamic assays
In support of clinical trials, our research group also focuses heavily on the development of pharmacodynamic assays, which could help us in diagnosis, but also in determining which patients benefit more from treatment.
These assays include the quantification of poly(ADP-ribose) polymerase (PARP) inhibition in peripheral blood mononuclear cells (PBMCs), which is currently validated in phase I clinical trials with the PARP-inhibitor olaparib, and circulating endothelial cells (CECs) in plasma.
Furthermore, we are in the process of validating a new assay to determine circulating tumor cells (CTCs) both in blood samples and in cerebrospinal fluid. With this assay, we could possibly detect signs of disease progression at an earlier stage.
Lastly, we are involved in optimizing assays for the determination of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) activity. These enzymes plays an important part in the metabolism and activity of fluoropyrimidines. Patients with decreased metabolism are at risk of developing serious toxicities and thus determining the DPD activity before starting treatment could warrant a dose adjustment.

Clinical pharmacology
In collaboration with our pharmacy department, our research groups conducts trials to test the safety and pharmacokinetics new oral formulations of intravenous anti-cancer drugs, such as docetaxel and paclitaxel.
Furthermore, to optimize treatment of tyrosine kinase inhibitors, we aim to develop and/or optimize therapeutic drug monitoring (TDM) for both new and existing anti-cancer treatments.
Additionally, the collaboration with the pharmacy also allows us to explore other types of pharmacological research, such as mass balance studies, measurements of intracellular metabolites of anti-cancer drugs and pharmacokinetic and pharmacodynamics modeling and simulation.



Mark van Bussel, MSc

Ph.D. Student


In 2013 I finished my Master in Pharmacy at Utrecht University. In my master research project I studied the pleiotropic effects of statins and ACE-inhibitors in patients with COPD at The University of Alabama at Birmingham, United States. Thereafter, I worked as a pharmacist in a hospital pharmacy. My projects focus on phase I/II clinical studies.

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Geenen, Jill

Jill Geenen, MSc, M.D.

Ph.D. Student


In 2012 I finished medical school at the University of Amsterdam cum laude. During medical school I did an internship oncology at the NKI. The first year after graduating I worked as a resident of internal medicine in Flevo Hospital. Hereafter I entered a resident training program to become an internist. The past eighteen months I worked as a resident in internal medicine. 
Due to increasing interest in research I decided to interrupt my residency. During my PhD studies I will focus on phase I/II clinical trials. My main focus will be the REVIVAL study of carboplatin-olaparib in BRCAm breast cancer patients.



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Heinhuis, Kimberley

Kimberley Heinhuis

Ph.D. Student


I studied medicine at VUmc. In July 2015 I obtained my master's degree and started working as ANIOS oncology at the SLAZ hospital for 9 months. My project in The Netherlands cancer institute consists of phase I clinical studies with nivolumab in combination with newer therapies.

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Huijberts, Sanne

Sanne Huijberts, MSc

Ph.D. Student


I finished medical school at the University of Amsterdam in january 2014. Hereafter I worked for 1 year as a resident in internal medicine at the AvL/NKI and for 8 months in Spaarne hospital. Due to my work in the clinic I became more and more interested in research, especially in oncology. I focus on phase I studies related to targeted therapy for BRAF mutated tumors.

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Dick Pluim, BSc



I am involved as an independent researcher in the development and validation of non-invasive predictive and pharmacodynamic biomarker assays for monitoring the effect of molecular targeted anticancer agents. These assays can be used to predict if a patient will benefit from a particular treatment. This work includes: 1. enzymatic activity assays for dihydropyrimidine dehydrogenase, thymidine synthase, and polyADPribose polymerase. 2. assays for the enumeration of circulating epithelial and melanoma tumor cells.



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Willeke Ros, MSc

Ph.D. Student


My name is Willeke Ros I have completed my bachelor in Biology and my master in Biomedical Sciences at Leiden University. During my studies I have performed various  internships focusing mostly on fundamental research questions. However, during my last internship at the University of Wisconsin-Madison, I did research which was part of clinical trials. I enjoyed the translational nature of the research and decided I wanted to continue doing clinical research. During my PhD studies I will focus on phase I/II clinical trials related to immunotherapy.

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Knikman, Jonathan

Jonathan Knikman

Ph.D. student


I finished my master in Pharmacy in April 2018 and shortly after started my PhD at the NKI-AVL. The main focus of my PhD will be improving the safety, feasibility and cost-effectiveness of genotype- and phenotype-directed individualized dosing of fluoropyrimidines.

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Key publications View All Publications

  • Upfront Genotyping of DPYD*2A to Individualize Fluoropyrimidine Therapy: A Safety and Cost Analysis

    (2015) J Clin Oncol. Nov 16. pii: JCO.2015.63.1325. [Epub ahead of print]

    Deenen MJ, Meulendijks D, Cats A, Sechterberger MK, Severens JL, Boot H, Smits PH, Rosing H, Mandigers CM, Soesan M, Beijnen JH, Schellens JH.

    Link to PubMed
  • Clinical relevance of DPYD variants c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity: a systematic review and meta-analysis of individual patient data

    (2015) Lancet Oncol. Oct 21. pii: S1470-2045(15)00286-7. doi: 10.1016/S1470-2045(15)00286-7. [Epub ahead of print]

    Meulendijks D, Henricks LM, Sonke GS, Deenen MJ, Froehlich TK, Amstutz U, Largiadèr CR, Jennings BA, Marinaki AM, Sanderson JD, Kleibl Z, Kleiblova P, Schwab M, Zanger UM, Palles C, Tomlinson I, Gross E, van Kuilenburg AB, Punt CJ, Koopman M, Beijnen JH, Cats A, Schellens JH.

    Link to PubMed

Recent publications View All Publications

  • Pharmacokinetics and excretion of 14C-omacetaxine in patients with advanced solid tumors

    (2016) Invest New Drugs. May 25. [Epub ahead of print]

    Nijenhuis CM, Hellriegel E, Beijnen JH, Hershock D, Huitema AD, Lucas L, Mergui-Roelvink M, Munteanu M, Rabinovich-Guilatt L, Robertson P Jr, Rosing H, Spiegelstein O, Schellens JH.

    Link to PubMed
  • Regulatory aspects of human radiolabeled mass balance studies in oncology: concise review

    (2016) Drug Metab Rev. May 17:1-15. [Epub ahead of print]

    Nijenhuis CM, Schellens JH, Beijnen JH.

    Link to PubMed


  • Office manager

    Lara Spee

  • Telephone Number

    +31 20 512 2035


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