Radiotherapy is still the mainstay and most effective treatment for the majority (~50 %) of all cancer patients. However, in recent years, there have been significant advancements, development and utilisation of alternative modes of radiotherapy. For example, proton beam therapy can precisely target the tumour and enhance normal tissue sparing, thus avoiding the adverse side effects commonly associated with conventional radiotherapy approaches. Furthermore, use of radiotherapy with increased linear energy transfer (LET), including heavy ions, can provide more optimal tumour control through enhanced relative biological effectiveness (RBE). As well as technological advancements, there has been novel discoveries particularly into the delivery of radiotherapy at ultra-high dose rates (FLASH) and minibeam radiotherapy that both promote a sparing effect on normal tissues, which are significant active areas for ongoing preclinical and clinical research. Moreover, identification of effective combinatorial approaches targeting important radiobiological factors including the cellular DNA damage response, hypoxic and immune modulation, as well as targeted nuclide radiotherapy, are continually under investigation using specific 2D/3D in vitro and in vivo tumour models.

In this Collection, we aim to present up-to-date overviews of the latest developments and preclinical research in the biological understanding of low- and high-LET radiation, leading to strategies to enhance tumour control whilst optimising normal tissue sparing. Topics of reviews for inclusion in this Collection include (but are not limited to):

• Comparative radiobiology of low versus high-LET (e.g. photon, proton and heavy ion) radiation. 

• Strategies for targeted molecular radionuclide therapy. 

• Optimisation of radiotherapy delivery (e.g. FLASH and minibeam radiation) through normal tissue sparing. 

• Normal tissue responses (e.g. acute and long-term toxicity) to low and high-LET radiation. 

• Targeting cellular pathways (e.g. DNA damage repair, hypoxia and the immune system) for enhancing radiotherapy efficacy. 

Guest Editor: Dr Jason Parsons (University of Liverpool, UK) who can be contacted at: J.Parsons@liverpool.ac.uk

Submission deadline: 30th June 2022