foto

Dr. N.A.P. Franken PhD

Position
Scientific staff member (UD)
Main activities
Research, Teaching
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 B, Uitterhoeve L, Oomen I, ten Cate R, Medema JP, Vrieling H, Stalpers LJA, Moerland PD, Franken NAP, Prostate Cancer Patients with Late Radiation Toxicity Exhibit Reduced Expression of Genes Involved in DNA Double-Strand Break Repair and Homologous Recombination. CANCER RES 2017;77 (6):1485-1491 [PubMed]
  • Oei AL, van Leeuwen CM, ten Cate R, Rodermond HM, Buist MR, Stalpers LJA, Crezee J, Kok HP, Medema JP, Franken NAP, Hyperthermia Selectively Targets Human Papillomavirus in Cervical Tumors via p53-Dependent Apoptosis. CANCER RES 2015;75 (23):5120-5129 [PubMed]
  • van Oorschot B, Granata G, Di Franco S, ten Cate R, Rodermond HM, Todaro M, Medema JP, Franken NAP, 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 JWJ, Krawczyk PM, Borovski T, ten Cate R, Rodermond HM, Stap J, Medema JP, Haveman J, Essers J, van Bree C, Stalpers LJA, Kanaar R, Aten JA, Franken NAP, 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 AL, Vriend LEM, van Leeuwen CM, Rodermond HM, ten Cate R, Westermann AM, Stalpers LJA, Crezee J, Kanaar R, Kok HP, Krawczyk PM, Franken NAP, 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

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

 

Faculty
Dr. N.A.P. Franken PhD

Postdocs
Dr. V. Ahire
Drs. A.L. Oei

PhD Students
F.C.P.A. Helderman MSc
M. Ijff MSc
A.C. Nuijens MD

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

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

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

Other research related activities
  • 1, Secretary/Treasurer Dutch Society for Radiobiology
  • 2, Member of the Council of the European Radiation Research Society
  • member, Netherlands Commission on Radiation Dosimetry
  • Membership of editorial board / Editorship, INTERNATIONAL JOURNAL OF HYPERTHERMIA
  • Membership of editorial board / Editorship, ONCOLOGY REPORTS
  • Membership of editorial board / Editorship, GENETICS
  • Membership of medical or scientific committee, International association of Radiation Research, council
  • Membership of medical or scientific committee, European Radiation Research Society, Scientific committee congres 2012, 2013, 2014, 2014, 2015, 2016
  • editor ISRN Oncology, Hindawi publishers
  • Membership of advisory board / Consultant, Stralenbescherming AMC
Current research funding
  • KWF Kankerbestrijding