Liverpool Cancer Research Centre and the Liverpool Head and Neck Centre Research Funding Success

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Two research projects led by Dr Jason Parsons have been granted funding totalling ~£2.2M from the NIH (National Institutes of Health) and the MRC (Medical Research Council).

The first of the projects is ‘Realizing the radiobiological impact of protons and high-LET particles in head and neck cancer and glioblastoma models’ which is examining the biological impact of proton beam therapy in cancer cells from the head and neck, but also of the adult brain and to devise effective strategies for tumour cell killing leading to a future improvement in patient response. The second being ‘Novel insights into the cellular response to complex DNA damage induced by proton beam therapy’ which is determining the effect of proton beam therapy on head and neck cancer cells at the molecular and DNA level, leading to future optimal treatments for patients.

Current research in Dr Parson’s lab is centred on investigating the biology of ionising radiation (radiotherapy) using tumour models, with a particular focus on head and neck cancers. Here they analyse the effects of conventional x-ray (photon) irradiation in Dr Parson’s lab at the University of Liverpool, but also comparisons against proton beam therapy at the Clatterbridge Cancer Centre. Proton beam therapy is advantageous since it is a precision radiotherapy technique that can deliver the majority of the radiation dose to the tumour, and limits the unnecessary irradiation of the surrounding normal, healthy cells and tissues in proximity to the tumour. This leads to reduced adverse side effects commonly observed with conventional radiotherapy. Nevertheless, the goal is to use research results to improve our basic understanding of radiation biology at the molecular and cellular level, but importantly to identify optimal strategies using radiotherapy (photons and protons) for more effective patient cancer treatment.

In the radiotherapy field, there is generally a good understanding of the biological effects of conventional (photon) irradiation, however in contrast, knowledge of the impact of proton beam therapy is less well advanced and where additional, essential research is necessary. The importance of proton beam therapy has been demonstrated by the recent £250M investment by the UK Government in establishing facilities in Manchester and London capable of delivering protons for cancer treatment, which will operate alongside the Clatterbridge Cancer Centre that is specifically for patients with eye tumours. The challenge is therefore to perform research centred on improving our basic understanding of the effects of proton versus photon irradiation on specific tumours, and where our research has a particular focus on cancers of the head and neck, and identify how this differs from the response of the normal tissues to the radiation dose.

Another challenge is that specific tumours, including sub-types of head and neck cancers, are resistant to the effects of radiotherapy. Therefore, there is an urgent need to determine targets within tumour cells, as well as the development of drugs or inhibitors against these targets, that can further enhance the effectiveness of radiotherapy in cancer treatment.

Dr Parsons who coordinates both of these projects stated: “I am extremely grateful to this recent funding from the NIH and the MRC which will help to support and expand on my Groups current radiation research activities. The ~£1.6M grant from NIH, which I will lead on, is a multi-centre award spanning the Universities of Liverpool, Birmingham, Oxford and Glasgow, and brings together world leading experts in radiation physics, biology and clinical oncology. The research in Liverpool will engage with the expertise of Prof Sonia Rocha in the Institute of Systems, Molecular and Integrative Biology and Prof Terry Jones via the Liverpool Head and Neck Centre. This will focus on utilising radioresistant cell models of head and neck cancers, but also brain tumours, and to understand the biological effects of proton beam therapy compared to conventional photon radiotherapy on these tumour models as well as on normal cells and tissues. We will analyse the impact of the radiation at the molecular (DNA) level to see how this correlates with cell survival. We will also analyse important factors such as reduced oxygen levels (hypoxia) which is important in contributing to tumour radiation resistance, but also the delivery of radiation at ultra-high dose rates where evidence suggests that this promotes normal tissue sparing. Finally, we aim to identify the combination of specific drugs and inhibitors that can be used in combination with radiotherapy, particularly protons, in optimising tumour cell killing.

“The ~£620k grant from MRC will concentrate our efforts on understanding the molecular effects of proton beam therapy in head and neck cancer cell models. The delivery of protons can lead to areas of extensive damage to the DNA within tumour tissues, which is a further significant advantage of this precision therapy compared to conventional radiotherapy. However, there is significant uncertainty as to how tumour cells respond to this extensive damage, particularly at the DNA level, and so our research will reveal molecular details on the proteins and mechanisms that respond to this.”

In the long term, this collaborative and multi-centre approach will promote more advanced and detailed knowledge of the effects of radiotherapy (with a focus on proton beam therapy) on tumours of the head and neck, but also the brain that are resistant to radiation treatment.

This will help physicists and biologists working in the radiation and cancer biology field to further enhance our level of scientific knowledge, but also help clinical oncologists to devise optimal treatment strategies using radiotherapy for cancer patients.