Research group Molecular prognostic and predictive factors in solid tumors

Aims

1. This group generally aims to discover causes of radioresistance and targets for radiosensitization.
2. The Radiotherapy & OncoImmunology (ROI) lab aims to optimize combined treatment of radiotherapy and immunotherapy, with the group focusing on optimal irradiation procedures (hypofracionation, partial tumor irradiation, lymph node sparing, etc).
3. We validate potential biomarkers for radioresistance/radiosensitivity in retrospective and prospective biobanks, aiming for patient selection and/or treatment optimization.
4. We are exploring the potential of combining external beam irradiation with targeted nuclear therapy.

Achievements

1. Much of our work has been directed at the main cause for resistance to radiotherapy, ie. hypoxia, and how oxygen breathing or oxydative phosphorylation inhibition might sensitize tumor to irradiation.
2. We participated in the International Cancer Genome Consortium (ICGC) and the Pan-Cancer Analysis of Whole Genomes Consortium (PCWAG), initiating the Radboud BreastCancer Biobank.
3. We investigated the cause and consequences of APOBEC3 dysregulation in breast cancer.
4. We found that tamoxifen treatment leads to radioresistance via its effect on mitochondria and ROS5) we found that localised irradiation (Head and Neck) induces a systemic anti-oxidant response.

Publications

See the publication list of the research group leader on Web of Science.

• A selection of our publications

  • Mitochondria Targeting of Oxidative Phosphorylation Inhibitors to Alleviate Hypoxia and Enhance Anticancer Treatment Efficacy DOI: 10.1158/1078-0432.CCR-24-3296
  • Clinical Implications of APOBEC3-Mediated Mutagenesis in Breast Cancer doi: 10.1158/1078-0432.CCR-22-2861.
  • Targeting Oxidative Phosphorylation to Increase the Efficacy of Radio- and Immune-Combination Therapy DOI: 10.1158/1078-0432.CCR-20-3913
  • The tumor microenvironment and radiotherapy response; a central role for cancer-associated fibroblasts DOI: 10.1016/j.ctro.2020.04.001
  • The mechanical microenvironment in cancer: How physics affects tumours DOI: 10.1016/j.semcancer.2015.09.001
  • Biology of hypoxia DOI: 10.1053/j.semnuclmed.2014.10.002
  • Tunable Hybrid Matrices Drive Epithelial Morphogenesis and YAP Translocation DOI: 10.1002/advs.202003380
  • Signatures of mutational processes in human cancer DOI: 10.1038/nature12477
  • Divergent mutational processes distinguish hypoxic and normoxic tumours DOI: 10.1038/s41467-019-14052-x
  • Characterizing OXPHOS inhibitor-mediated alleviation of hypoxia using high-throughput live cell-imaging DOI: 10.1186/s40170-024-00342-6