Development of innovative proton and neutron therapies with high cancer specificity by 'hijacking' the intracellular chemistry of haem biosynthesis.

Introduction

Deep-lying cancers, such as glioblastoma multiforme (GBM) brain cancer, are very difficult to access and incurable by the current standards of care. The fluorescence of photosensitive molecules (PSs) can precisely guide surgical resection of GBM.

Limitations of Current Treatments

Nevertheless, photomedical treatments like photodynamic therapy (PDT) show limited efficacy due to the low penetration of light into tissue. Proton radiotherapy can reach deep-lying disease through therapeutic energy deposition in a spatially confined region called the Bragg peak. Current neutron-based therapies, like Boron Neutron Capture Therapy (BNCT), have sufficient penetration depth but lack cancer specificity.

Project Proposal

In NuCapCure, we propose to 'hijack' intracellular biosynthetic pathways and use them to produce custom-made drugs that will facilitate two genuinely new cancer treatments:

1. "NuCapCure Proton": This treatment combines proton radiotherapy, protondynamic therapy through PS proton activation, and proton capture therapy (BPCT) through three produced alpha particles.
2. "NuCapCure Neutron": This treatment combines GBM-specific BNCT and PS neutron activation as demonstrated in our FET-open project FRINGE.

Scientific Breakthroughs

The main scientific breakthroughs of NuCapCure will be to demonstrate the custom production of novel compounds through native intracellular biosynthesis. Additionally, we aim to establish experimental proof-of-principle, both in vitro and in vivo, of the proposed two novel therapies.

Interdisciplinary Team

Our highly interdisciplinary project team comprises world-renowned experts from a unique combination of disciplines:

• Proton and neutron physics
• Synthetic chemistry
• Photochemistry
• Photobiology
• Radiobiology
• Medical physics
• Nuclear reactor and particle accelerator technology
• Radio-oncology

This collaboration aims to lay the foundations for novel, targeted, and curative therapies against currently fatal cancer indications like GBM.