Marika Nestor – Novel cancer-targeting strategies for improved molecular radiotherapy

Molecular radiotherapy has revolutionised the treatment of several malignancies in recent years. However, treatment of solid tumours has been hampered by dose-limiting toxicities and tumour radioresistance.

The aim of our research is to develop novel radiolabelled cancer targeting agents and radio-sensitisation strategies for improved molecular cancer diagnostics and therapy. To enable this, targeting molecules towards cancer-associated targets are generated, radiolabelled and further evaluated and developed for use in precision imaging, theranostics, and molecular radiotherapy. Moreover, novel strategies to potentiate therapeutic effects of radiotherapy are evaluated in combination with radiotherapy in order to assess potential synergistic effects.

Increasing the effect of radiotherapy

Radio-sensitising strategies include molecules that enhance p53-mediated apoptosis or prevents DNA repair. Molecular combination effects, therapeutic efficacy, and potential toxicity are assessed both in vitro and in vivo. Model systems span from immortalized and primary single cancer cells to tumour spheroids and xenografts. We also characterize protein-cell interactions using a novel class of biosensor that detects how proteins bind to cells in real-time.

Improved radiotherapy with fewer side effects

Ultimately, our cancer targeting radiopharmaceuticals could be clinically applied to non-invasively characterise and image cancer cells, stratify patients, monitor treatment response, as well as for molecular radiotherapy. Moreover, radio-sensitisation strategies may be applied to improve outcomes of radiotherapy, enabling more effective radiation treatments, potentially also reducing radiation exposure and undesirable side effects in normal tissues.

In time, we hope that our research will contribute to improving radiotherapy treatment outcomes and prolong cancer patient survival.

Drawing illustrating the concept of radio-immunotargeting
The concept of radio-immunotargeting
A radiolabeled compound binds to a target that is overexpressed on the surface of tumor cells, while normal cells do not (or to very small extent) express the target. Thus, the radionuclide will accumulate on tumor cells but not in normal tissue.