5 PhDs for INTO-PROT: Improving proton therapy in brain, head and neck cancer

The INTO-PROT Consortium is looking for five ambitious PhD-students ready to start their research projects by June 2019.

INTO-PROT is a 4-year collaborative research project aiming at further increasing therapeutic window of proton therapy of cancer funded by a Dutch Cancer Society Consortium grant.
Proton/particle therapy is currently mainly used to prevent radiation-induced side effects. However, to achieve the full exploitation of the advantages of proton therapy knowledge on biological mechanisms of tumor and normal tissue response are urgently needed.
The project will investigate and develop future options for proton therapy, focussing on brain and head and neck tumours and normal tissue, covering about 30% of all PT indications. We will study which mechanisms underlie the different damage responses to photon and proton radiation in tumour and normal tissue by studying: DNA repair kinetics, molecular signatures, (stem) cellular sensitivity, biomarkers of immune response and tissue response to protons at different linear energy transfer. Furthermore, the added value of combining proton/particle therapy with response modulators will be studied, including DNA repair modifiers, hypoxia activated drugs, immunotherapy as well as hyperthermia. Better understanding of the mechanisms of damage will allow optimisation of proton therapy combined with the use of novel and existing combination therapies with the intention is to improve tumour control without additional risk of unwanted side-effects, and hence further improving survival and/or quality of life for cancer patients.

For more information please follow this link.

2 PhD students and 1 PostDoc at Radboud UMC


PhD ‘Metabolism modulation with immunotherapy and radiotherapy’ (project 1)

Tumor hypoxia has a negative impact on treatment outcome via direct radioresistance of hypoxic cells and poor perfusion of hypoxic areas. In addition, hypoxia provides a niche for clonogenic tumor stem cells and induces and sustains immunosuppression. Aim of this project is to improve the efficacy of the combination of high dose stereotactic radiotherapy and immune modulation by reducing tumor hypoxia and metabolic engeneering. Syngenic tumor models will be fully mapped using immunohistochemistry with semi-automated image analysis, FACS analysis and tumor monitoring by means of PET/SPECT imaging.

PhD ‘Understanding cGAS activation to improve Immuno-radiotherapy combinations’ (project 2)

The cGAS/Sting pathway links radiotherapy to immune activation. Potent immune response induction, however, requires immunogenic cell death and triggering of multiple immune activation pathways simultaneously. Aim of this project is to understand cGAS activation, to define immune pathways synergizing with cGAS and to define tumor ablative regimens optimal for Immuno-radiotherapy combinations. Immunological/Cell-biological approaches (FACS/functional assays, Transfection/Crispr/CAS, Microscopy) will be combined with syngeneic tumor models and state of the art tumor ablation technologies.

PostDoc

For the ROI laboratory we are also looking for an Postdoc position. See for more information our vacancy on the website. Upon malignant transformation, tumor cells upregulate the synthesis of sialic acid sugar-carrying glycans (sialoglycans). These sialic acids not only promote tumor cell growth but also protect them from recognition and eradication by immune cells. In this project novel human Siglec blocking mAbs will be tested in functional immunological assays and IHC in healthy donors and cancer patients.

For more information follow this link.