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Realizing the radiobiological impact of protons and high-LET particles in head and neck cancer and glioblastoma models

Award Number: R01CA256854
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Realizing the radiobiological impact of protons and high-LET particles in head and neck cancer and glioblastoma models - Project Summary Radiotherapy is still one of the most effective cancer treatments used to treatment ~50 % of all human cancers, and particularly solid tumours of the head and neck and brain. However, acute and long term adverse side effects of radiotherapy are still common, and some tumours are also resistant to the therapeutic effects of the radiation. The increased use of precision particle radiotherapy, particularly proton beam therapy, enables the radiation dose to be delivered precisely to the tumour, which spares the surrounding normal tissues of any unwanted radiation dose and is therefore able to limit some of the adverse side effects. Furthermore, the ability to deliver radiation that causes extensive damage to the tumour tissues (so called “high-LET”) is also a significant advantage in effective radiotherapy. However despite this, there is still uncertainty regarding the biological effects of protons and high-LET radiation on both normal and tumour cells and tissues, and how the radiotherapy can be optimised for patient benefit. This proposal brings together world leading experts in radiation physics, biology and clinical oncology to reveal new knowledge of the biological impact of protons and high-LET radiation versus conventional (x- ray) radiotherapy, on cell models of head and neck and brain tumours. This will be performed on both 2- dimensional, but also 3-dimensional cell models of the tumours which are more similar to those observed in patients. We will thoroughly analyse the precise effect of protons and high-LET radiation at the molecular (DNA) level, and how this correlates with the impact on overall survival of the cells. We will also investigate the role of important factors such as low oxygen levels (hypoxia) which is important in driving resistance of solid tumours of the head and neck and brain to radiotherapy, but also the rate at which the radiotherapy is delivered (particularly high dose rates, so called “FLASH”), on the biology and survival of the tumour versus the normal cells. Additionally, we will identify the combination of specific drugs and inhibitors under the various conditions that are more effective in combination with protons and high-LET radiation in optimising tumour cell killing, whilst sparing the associated normal cells. In the long term, our research will contribute to the identification and development of more effective strategies using radiotherapy, including proton beam therapy, for tumours of the head and neck and brain that are particularly resistant to the radiation treatment. This will lead to an improvement in the patient response but also in overall survival following precision particle radiotherapy. 1


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $300,832 )
2025	2025	UNIVERSITY OF BIRMINGHAM	EDGBASTON	BIRMINGHAM				GBR	Cancer Treatment Research	000	5	4/4/2025	NON-COMPETING CONTINUATION	$300,832
														Subtotal = $300,832

Issue Date FY: 2024 ( Subtotal = $318,154 )
2024	2024	UNIVERSITY OF BIRMINGHAM	EDGBASTON	BIRMINGHAM				GBR	Cancer Treatment Research	004	4	5/15/2024	NON-COMPETING CONTINUATION	$318,154
2024	2023	UNIVERSITY OF BIRMINGHAM	EDGBASTON	BIRMINGHAM				GBR	Cancer Treatment Research	002	3	4/11/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$329,211
2024	2023	UNIVERSITY OF BIRMINGHAM	EDGBASTON	BIRMINGHAM				GBR	Cancer Treatment Research	003	3	4/15/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$329,211
2024	2023	UNIVERSITY OF BIRMINGHAM	EDGBASTON	BIRMINGHAM				GBR	Cancer Treatment Research	000	3	2/9/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$329,211
2024	2023	UNIVERSITY OF BIRMINGHAM	EDGBASTON	BIRMINGHAM				GBR	Cancer Treatment Research	001	3	2/13/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$329,211
														Subtotal = $318,154

Issue Date FY: 2023 ( Subtotal = $329,211 )
2023	2023	UNIVERSITY OF BIRMINGHAM	EDGBASTON	BIRMINGHAM				GBR	Cancer Treatment Research	001	3	9/21/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$329,211
2023	2022	UNIVERSITY OF LIVERPOOL	FOUNDATION BUILDING, 765 BROWNLOW HILL	LIVERPOOL				GBR	Cancer Treatment Research	000	2	9/21/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $329,211

Issue Date FY: 2022 ( Subtotal = $328,710 )
2022	2022	THE UNIVERSITY OF LIVERPOOL	BROWNLOW HILL	LIVERPOOL	MERSEYSIDE			GBR	Cancer Treatment Research	000	2	4/14/2022	NON-COMPETING CONTINUATION	$328,710
														Subtotal = $328,710

Issue Date FY: 2021 ( Subtotal = $430,702 )
2021	2021	THE UNIVERSITY OF LIVERPOOL	BROWNLOW HILL	LIVERPOOL	MERSEYSIDE			GBR	Cancer Treatment Research	000	1	6/30/2021	NEW	$430,702
														Subtotal = $430,702

Grand Total All Awards = $1,707,609

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Realizing the radiobiological impact of protons and high-LET particles in head and neck cancer and glioblastoma models

Award Number: R01CA256854

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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