Radiation Oncology

Research projects

Microbeam Radiation Therapy-induced vascular permeability window and nanoparticle-enhanced therapy

Djonov group  Prof. Dr. med. Valentin Djonov

Microbeam Radiation Therapy delivers arrays of ultra-narrow X-ray beams that generate steep dose heterogeneity within tissues.
This geometry allows exceptional normal-tissue tolerance while maintaining strong tumour control.
Our research investigates how Microbeam Radiation Therapy temporarily increases tumour vascular permeability, creating a “permeability window” that enables enhanced delivery of nanoparticles or therapeutic agents.

Using synchrotron microbeam arrays in melanoma models, we demonstrated that a priming exposure of 150 Gy increases intratumoural gold-nanoparticle accumulation more than twofold and, when combined with a therapeutic microbeam dose (400 Gy peaks), significantly delays tumour growth and extends survival.
Image Mass Cytometry revealed nanoparticle localisation near tumour vessels and in M2-like macrophages, confirming a transient vascular-permeability mechanism.

This project builds on the first report of this phenomenon (Sabatasso et al., Cancers 2021; DOI: 10.3390/cancers13092103), which established a 15-min to 4-h permeability window suitable for adjuvant delivery, and the concept is protected under patent ref. P166072 (“Microbeam Radiation Therapy–induced vascular permeability window for drug delivery”).
We are now defining the dosimetric and biological parameters that govern this effect and testing whether similar windows can be achieved with compact sub-millimetre sources compatible with clinical translation.
Our long-term goal is to integrate this mechanism into combination radiotherapies that enhance radiosensitisation, immunotherapy efficacy, and targeted drug delivery in radio-resistant tumours.
Microbeam Radiation Therapy–induced vascular permeability enables gold-nanoparticle delivery and improves tumour control. (A) Quantification of gold nanoparticle (AuNP) uptake in B16-F10 melanomas five days after a 150 Gy priming MRT array shows more than twofold enhancement compared with non-primed controls. (B) 3-D micro-CT reconstructions reveal higher intratumoural AuNP accumulation after priming. (C–C′) Image Mass Cytometry visualizes AuNPs (yellow) adjacent to CD31⁺ vessels (green) and within CD206⁺ M2-like macrophages (red), mainly at the tumour periphery; Collagen-I and Vimentin are shown in white and blue. (D) Kaplan–Meier survival curves demonstrate significant survival benefit (log-rank p < 0.0001) when priming MRT is combined with AuNPs and therapeutic MRT (400 Gy peaks). (E) Median survival times (days): 150MRT + Au + 400MRT = 39.5, 150MRT + 400MRT = 29, Au + 400MRT = 25, 400MRT = 18, 150MRT + Au = 11.5, Control = 6. Together, panels A–E illustrate that MRT opens a transient vascular permeability window that enhances nanoparticle delivery and potentiates therapeutic outcome. Source: Fernandez-Palomo C et al., Int J Radiat Oncol Biol Phys (2025) doi:10.1016/j.ijrobp.2025.07.1427.

Targeting cellular metabolism to augment cancer therapy

Inhibition of lactate metabolism selectively damages the mitochondria of cancer cells, and when combined with radiotherapy, leads to a marked reduction in tumor growth in a mouse model of NSCLC – Reference source: Deng H. et al., 2025 (https://www.nature.com/articles/s41467-025-57906-3)

Marti Group PD Dr. med. Thomas Marti

The aim of this project is to investigate how the nucleotide/lactate metabolism and the DNA damage response machinery are associated with the tumor initiating capacity, the chemotherapy response, and the metastatic capacity of lung and mesothelioma cancer stem cells. In addition, we are exploiting treatment induced cellular adaptations as novel targets for cancer therapy.

 

Oncogenic signaling via receptor tyrosine kinases in crosstalk with DNA damage repair

Primary structure of the MET receptor. The studied MET Ser1016 phosphorylation site is located in the juxtamembrane region. – Reference source: Medova lab (courtesy of Liana Hayrapetyan)

Medová Group PD Dr. med. Michaela Medová

Tyrosine kinase receptors activate a wide range of different cellular signaling pathways. Physiologically, intact signaling via the MET receptor is indispensable in embryonic development and tissue homeostasis. At the same time, MET dysregulation promotes features clearly associated with tumor growth and progression such as uncontrolled proliferation, angiogenesis, local invasion, and systemic dissemination. 

Accumulating data suggest that MET signaling may also protect tumor cells from DNA damage, hence relating its aberrant activity to resistance to DNA-damaging agents routinely used in cancer treatment. 

We have identified a previously unreported phosphorylation site on MET, which can be recognized by DNA damage master kinases and is involved not only in cellular responses towards DNA damage, but also in metastatic processes, cancer cell migration, and anchorage-independent growth. 

This project aims at dissecting the nature, function, and regulation of this phosphorylation site in oncogenic signaling of the receptor.

 

Artificial Intelligence for Automated QUality Assurance in RadioTherapy for glioblastoma target volume and organs at risk delineation in clinical trials - AQUA RT

Schematic of the proposed AQUA RT for automated delineation quality assurance in glioblastoma patients. Top part shows the current manual delineation, which is compared to the proposed AQUA RT approach (bottom part).

Reyes group Prof. Dr. Mauricio Reyes

In this project we aim to test the hypothesis that AI-based auto-segmentation technologies can be used for an AI-assisted multi-criteria quality assurance assessment in radiation therapy. The proposed multicriteria evaluation model is expected to provide a more objective review than traditional approaches, while at the same time focussing on clinically relevant radiotherapy aspects. The proposed Automated QUality Assurance in RadioTherapy (AQUA-RT) framework has the potential to increase consistency, improve delineation quality and reduce workload for routinely challenging quality assurance procedures.