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of the original HNSCC from which they were obtained. Whilst 3D spheroids can be developed from
the current HNSCC cell lines that exist [Table 1], these should be utilised more routinely in research.
However, there is a current lack of availability of patient-derived HNSCC organoids although some have
recently been reported [105,106] . Additionally, radiosensitisation strategies should be investigated in in vivo
models, particularly xenografts of HNSCC, to provide clear evidence that targeted inhibitors are effective
at suppressing or preventing HNSCC tumour growth. Another interesting aspect to examine is the impact
of particle beam therapy (e.g., protons and carbon ions) both alone and in combination with targeted
inhibitors. As we detailed earlier, these data are currently sparse, mainly due to limited access to the
appropriate resources, although there is some evidence to suggest that protons in particular may have a
different impact on the DNA damage spectra induced compared to conventional photon irradiation, and
thus may respond differently to combinations with DNA repair and DNA damage checkpoint inhibitors.
Similarly, the impact of increasing LET at and around the Bragg peak and the effect of higher-LET
radiation, including carbon ions, has yet to be thoroughly investigated. Nevertheless, once this extensive
preclinical data has been acquired for clearly identifying effective strategies in combination with RT (photons
and particle ions) for HNSCC, this will pave the way forward for future Phase I/II clinical trials.

DECLARATIONS
Authors’ contributions
Original draft preparation: Fabbrizi MR
Review and editing: Fabbrizi MR, Parsons JL

Availability of data and materials
Not applicable.

Financial support and sponsorship
Fabbrizi MR and Parsons JL are supported by North West Cancer Research (No. CR1197).

Conflicts of interest
Both authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.

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