foto

N.A.P. Franken PhD

Position
Research Associate
Main activities
Education, Research, Other
Specialisation
Radiobiology
Focus of research

 

1)  Sensitization of radiotherapy by hyperthermia combined with chemotherapeutic agents. To increase effects radiation can be sensitized with hyperthermia and/or chemotherapy. In the laboratory these sensitization effects are investigated. Especially agents that inhibit or interfere with DNA damage repair are a main topic. In ther study hyperthermia is also combined with small molecules like PARP1 inhibitors and/or chemotherapeutic agents e.g. cisplatin to sensitize radiation treatment.

 

2)Radiation sensitization effects of hyperthermia. Hyperthermia is one of the best sensitizers of radiotherapy. Hyperthermia treatment of cancer is increasing the temperature of the tumor up to 41- 43 C. Radiotherapy (ionizing radiation) induces DNA lesions. The most severe lesions are DNA double strand breaks (DSB). These DSB are repaired by two major repair pathways, Non-Homologous end-joining (NHEJ) and Homologous Recombination repair (HR). Hyperthermia treatment of 1 h at 42 C can inhibit the HR repair via a transient degradation of the BRCA2 protein which one of the major proteins of this pathway. In the laboratory we investigate the biological effects of hyperthermia in in vitro cell cultures. One of the the research topics is the study of the DNA damage repair pathway. DNA repair proteins that accumulate at the sites of the DSB are studied with fluorescently labelled antibodies and studied with the fluorescence microscope.

3) Development of tests to predict normal tissue damage after Radiotherapy and/or Hyperthermia. Normal tissue damage after radiotherapy is a major problem in the clinic. Therefore in the lab special markers are investigated that can predict late normal tissue damage. n.a.franken@amc.uva.nl

 

Key publications
  • van Oorschot Bregje, Uitterhoeve Lon, Oomen Ilja, ten Cate Rosemarie, Medema Jan Paul, Vrieling Harry, Stalpers Lukas J. A., Moerland Perry D., Franken Nicolaas A. P. Prostate Cancer Patients with Late Radiation Toxicity Exhibit Reduced Expression of Genes Involved in DNA Double-Strand Break Repair and Homologous Recombination Cancer research 2017;77 (6):1485-1491 [PubMed]
  • Oei Arlene L., van Leeuwen Caspar M., ten Cate Rosemarie, Rodermond Hans M., Buist Marrije R., Stalpers Lukas J. A., Crezee Johannes, Kok H. Petra, Medema Jan Paul, Franken Nicolaas A. P. Hyperthermia Selectively Targets Human Papillomavirus in Cervical Tumors via p53-Dependent Apoptosis Cancer research 2015;75 (23):5120-5129 [PubMed]
  • van Oorschot Bregje, Granata Giovanna, Di Franco Simone, ten Cate Rosemarie, Rodermond Hans M., Todaro Matilde, Medema Jan Paul, Franken Nicolaas A. P. Targeting DNA double strand break repair with hyperthermia and DNA-PKcs inhibition to enhance the effect of radiation treatment Oncotarget 2016;7 (40):65504-65513 [PubMed]
  • Bergs Judith W. J., Krawczyk Przemek M., Borovski Tijana, ten Cate Rosemarie, Rodermond Hans M., Stap Jan, Medema Jan Paul, Haveman Jaap, Essers Jeroen, van Bree Chris, Stalpers Lukas J. A., Kanaar Roland, Aten Jacob A., Franken Nicolaas A. P. Inhibition of homologous recombination by hyperthermia shunts early double strand break repair to non-homologous end-joining DNA repair 2013;12 (1):38-45 [PubMed]
  • Oei Arlene L., Vriend Lianne E. M., van Leeuwen Caspar M., Rodermond Hans M., ten Cate Rosemarie, Westermann Anneke M., Stalpers Lukas J. A., Crezee Johannes, Kanaar Roland, Kok H. Petra, Krawczyk Przemek M., Franken Nicolaas A. P. Sensitizing thermochemotherapy with a PARP1-inhibitor Oncotarget 2017;8 (10):16303-16312 [PubMed]
All Publications
Curriculum Vitae

Cozzarelli-prijs voor biologische wetenschappen van de National Academy of Science of the USA als een van de medeauteurs voor het artikel: Mild hyperthermia inhibits homologous recombination, induces BRCA2 degradation, and sensitizes cancer cells to poly(ADP-ribose) polymerase-1 inhibition (PNAS 2011)

KWF project UVA 2015-7820 Hyperthermia induced synthetic lethality combined with PARP1 inhibition to sensitize radiotherapy and cisplatin treatment of cervical carcinoma

KWF project UVA 2012-5540 Towards biological treatment planning in radiotherapy combined with hyperthermia to improve clinical outcome

KWF project UVA 2008-4019 Investigation of a gene set classifier for late radiation tocicity in prostate cancer patients

Vanderes project 234: De DNA schade respons en hypoxie in locaal recidieven van borsttumoren na radiotherapie en hyperthermie

Research programmes

N.A.P. Franken PhD (Combined ionizing radiation and hyperthermia treatment to improve cancer therapy)

Research themes: 

1) Radiation sensitization effects of hyperthermia. Hyperthermia is one of the best sensitizers of radiotherapy. Hyperthermia treatment of cancer is increasing the temperature of the tumor up to 41- 43 C. Radiotherapy (ionizing radiation) induces DNA lesions. The most severe lesions are DNA double strand breaks (DSB). These DSB are repaired by two major repair pathways, Non-Homologous end-joining (NHEJ) and Homologous Recombination repair (HR). Hyperthermia treatment of 1 h at 42 C can inhibit the HR repair via a transient degradation of the BRCA2 protein which one of the major proteins of this pathway. In the laboratory we investigate the biological effects of hyperthermia in in vitro cell cultures. One of the the research topics is the study of the DNA damage repair pathway. DNA repair proteins that accumulate at the sites of the DSB are studied with fluorescently labelled antibodies and studied with the fluorescence microscope.

2) Sensitization of radiotherapy by hyperthermia combined with chemotherapeutic agents. To increase effects radiation can be sensitized with hyperthermia and/or chemotherapy. In the laboratory these sensitization effects are investigated. Especially agents that inhibit or interfere with DNA damage repair are a main topic. In ther study hyperthermia is also combined with small molecules like PARP1 inhibitors and/or chemotherapeutic agents e.g. cisplatin to sensitize radiation treatment. 

3) Development of tests to predict normal tissue damage after Radiotherapy and/or Hyperthermia. Normal tissue damage after radiotherapy is a major problem in the clinic. Therefore in the lab special markers are investigated that can predict late normal tissue damage. 

KWF project UVA 2015-7820 Hyperthermia induced synthetic lethality combined with PARP1 inhibition to sensitize radiotherapy and cisplatin treatment of cervical carcinoma

KWF project UVA 2012-5540  Towards biological treatment planning in radiotherapy combined with hyperthermia to improve clinical outcome

KWF project UVA 2008-4019 Investigation of a gene set classifier for late radiation tocicity in prostate cancer patients

Vanderes project 234: De DNA schade respons en hypoxie in locaal recidieven van borsttumoren na radiotherapie en hyperthermie

 

Postdocs
V. Ahire PhD
A.L. Oei PhD

Others
H.M. Rodermond BEng
R. ten Cate BEng

Prof. J.P. Medema PhD (Cell death induction and resistance in tumor cells)

Prof. C.R.N. Rasch PhD (Image guided and physics application in the clinic)

Current research funding
  • KWF Kankerbestrijding