Research interest
The research activities of our group extends on the interface between laboratory and clinic. It focuses on (1) the identification of novel targets and agents to increase the cytotoxic effect of radiation and on (2) the validation of new endpoints to quantify and predict the efficacy and toxicity of new combination therapies. The ultimate goal is to translate these strategies into clinical application.
In close collaboration with several research groups within the NKI, new agents are identified on the basis of their mechanism of action and subsequently tested for their ability to induce apoptotic cell death and to increase the cytotoxic effect of radiation in vitro and in vivo. These include synthetic alkylphospholipids, death receptor ligands (TRAIL, CD95L), small molecule inhibitors of Bcl-2 (Gossypol) and PARP inhibitors (APO866). The oral alkyl-phospholipid Perifosine combined with radiotherapy represents a strategy that we have advanced into the clinic.
To monitor tumor response and predict treatment outcome, we explore new functional imaging modalities. For example, in vivo imaging of apoptosis by annexin V scintigraphy was shown to be successful in predicting outcome after radiotherapy and/or chemotherapy in various tumor types. This imaging modality also allows to verify the mechanism of action of novel apoptosis-modulating strategies in vivo.
Another field of interest is the improvement of combination treatment of chemotherapy and radiation. For several types of solid tumors it has been shown that the combined use of both modalities improves outcome. Malignant tumors arising in the gastrointestinal tract in particular benefit from this combined approach. Optimization of the treatment of gastric cancer is currently one of our main focuses.
Key publications
Kartachova M, van Zandwijk N, Burgers S, van Tinteren H, Verheij M, Valdes Olmos RA (2007). Prognostic Significance of 99mTc Hynic-rh-Annexin V Scintigraphy During Platinum-based Chemotherapy in Advanced Lung Cancer. J Clin Oncol 25, 2534-2539.
Wissink EHJ, Verbrugge I, Vink SR, Schader MB, Schaefer U, Walczak H, Borst J, Verheij M (2006). TRAIL enhances efficacy of radiotherapy in a p53 mutant, Bcl-2 overexpressing lymphoid malignancy. Radiother Oncol 80, 214-222.
Vink SR, Schellens JHM, Beijnen JH, Sindermann H, Engel J, Dubbelman R, Moppi G, Hillebrand MJX, Bartelink H, Verheij M (2006). Phase I and pharmacokinetic study of combined treatment with study perifosine and radiation in patients with advanced solid tumours. Radiother Oncol 80, 207-213.
Vink SR, Lagerwerf S, Mesman E, Schellens JHM, Begg AC, van Blitterswijk WJ, Verheij M (2006). Radiosensitization of squamous cell carcinoma by the alkylphospholipid Perifosine in cell culture and xenografts. Clin Cancer Res 12, 1615-1622.
Jansen EPM, Boot H, Verheij M, van de Velde CJH (2005). Optimal locoregional treatment in gastric cancer. J Clin Oncol 23, 4509-4517.
Van Blitterswijk WJ, Koning GA, van Hell A, Vink S, Zerp S, Storm G, Verheij M Veldman RJ (2005). Co-formulated N-octanoyl-glucosylceramide improves cellular delivery and cytotoxicity of liposomal doxorubicin. J Pharmacol Exp Ther 315, 705-710.
Haas R, de Jong D, Valdés Olmos RA, Zerp SF, van den Heuvel I, Bartelink H, Verheij M (2004). In vivo imaging of radiation-induced apoptosis in follicular lymphoma patients. Int J Radiat Oncol Biol Phys 59, 782-787.
Van der Luit AH, Budde M, Ruurs P, Verheij M, van Blitterswijk WJ (2002). Alkyl-lysophospholipids induce apoptosis via raft-mediated endocytosis and inhibition of phosphatidylcholine synthesis. J Biol Chem 277, 39541-39547.
Ruiter GA, Zerp SF, Bartelink H, van Blitterswijk WJ, Verheij M (1999). Alkyl-lysophospholipids activate the SAPK/JNK pathway and enhance radiation-induced apoptosis. Cancer Res 59, 2457-2463.
Verheij M, Bose R, Lin XH, Yao B, Jarvis WD, Grant S, Birrer MJ, Szabo E, Zon LI, Kyriakis JM, Haimovitz-Friedman A, Fuks Z, Kolesnick RN (1996). Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis. Nature 380, 75-79.
Bose R, Verheij M, Haimovitz-Friedman A, Scotto K, Fuks Z, Kolesnick R (1995). Ceramide synthase mediates daunorubicin-induced apoptosis: an alternative mechanism for generating death signals. Cell 82, 405-414.
More publications by Marcel Verheij on PubMed
Biographic sketch
Marcel Verheij (1962) received his medical degree in 1989 at the State University in Leiden. Following his Military Service, he joined the Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital in Amsterdam where he did his residency in Radiation Oncology under supervision of Harry Bartelink. From 1994 until 1996 he joined the group of Zvi Fuks at Memorial Sloan-Kettering Cancer Center in New York as part of his PhD program. Here, he was involved in apoptosis research and studied the role of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) signal transduction pathway in radiation-induced apoptosis. In 1996 he received his PhD (cum laude) from the Free University in Amsterdam on Radiation Injury of the Kidney: Mechanisms and Modulation of Endothelial Dysfunction. Since 2000 he is a permanent staff radiation oncologist at the Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital where he holds a 50% clinical/50% research position. He is group leader at the Division of Cellular Biochemistry and coordinator of the clinical unit for combined modality treatment. In 2004 he was appointed professor in Translational Radiotherapy at the Free University in Amsterdam and since May 2007 he chairs the Department of Radiotherapy.
Co-workers
Borst, Jannie PhD Senior co-investigator
Van Blitterswijk, Wim PhD Senior co-investigator
Alderliesten, Maaike PhD Post-doc
Rooswinkel, Rogier MSc Graduate Student
Verbrugge, Inge MSc Graduate student
Zerp, Shuraila Technical staff
Van Klarenbeek, Jeffrey Technical staff
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