Proton and photon radiosensitization effects of niraparib, a PARP-1/-2 inhibitor, on human head and neck cancer cells

Li Wang; Jianzhong Cao; Xiaochun Wang; Eric Lin; Zeming Wang; Yuting Li; Yupeng Li; Mei Chen; Xianliang Wang; Bo Jiang; Ruiping Zhang; Narayan Sahoo; Xiaodong Zhang; X. Ronald Zhu; Jeffrey N. Myers; Steven J. Frank

doi:10.1002/hed.26155

Proton and photon radiosensitization effects of niraparib, a PARP-1/-2 inhibitor, on human head and neck cancer cells

Li Wang, Jianzhong Cao, Xiaochun Wang, Eric Lin, Zeming Wang, Yuting Li, Yupeng Li, Mei Chen, Xianliang Wang, Bo Jiang, Ruiping Zhang, Narayan Sahoo, Xiaodong Zhang, X. Ronald Zhu, Jeffrey N. Myers, Steven J. Frank

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Background: Combining photon or proton radiotherapy with targeted therapy shows promise for head and neck cancer (HNSCC). The poly (adenosine diphosphate [ADP]-ribose) polymerase-1/2 inhibitor niraparib targets DNA damage repair (DDR). We evaluated the effects of niraparib in combination with photons or protons, and its effects on the relative biological effectiveness (RBE) of protons, in human HNSCC cell lines. Methods: Radiosensitivity was assessed and RBE was calculated with clonogenic survival assays; unrepaired DNA double-strand breaks were evaluated using immunocytochemical analysis of 53BP1 foci. Results: Niraparib reduced colony formation in two of the four cell lines tested (P <.05), enhanced radiosensitivity in all four cell lines, delayed DDR (P <.05), and increased proton vs photon RBE. Conclusion: Niraparib enhanced the sensitivity of four HNSCC cell lines to both photons and protons and increased the RBE of protons, possibly by inhibiting DDR. Niraparib may enhance the effectiveness of both photon and proton radiotherapy for patients with HNSCC.

Original language	English (US)
Pages (from-to)	2244-2256
Number of pages	13
Journal	Head and Neck
Volume	42
Issue number	9
DOIs	https://doi.org/10.1002/hed.26155
State	Published - Sep 1 2020

Keywords

PARP inhibitor
head and neck cancer
proton radiotherapy
radiosensitivity
relative biological effectiveness

ASJC Scopus subject areas

Otorhinolaryngology

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10.1002/hed.26155

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title = "Proton and photon radiosensitization effects of niraparib, a PARP-1/-2 inhibitor, on human head and neck cancer cells",

abstract = "Background: Combining photon or proton radiotherapy with targeted therapy shows promise for head and neck cancer (HNSCC). The poly (adenosine diphosphate [ADP]-ribose) polymerase-1/2 inhibitor niraparib targets DNA damage repair (DDR). We evaluated the effects of niraparib in combination with photons or protons, and its effects on the relative biological effectiveness (RBE) of protons, in human HNSCC cell lines. Methods: Radiosensitivity was assessed and RBE was calculated with clonogenic survival assays; unrepaired DNA double-strand breaks were evaluated using immunocytochemical analysis of 53BP1 foci. Results: Niraparib reduced colony formation in two of the four cell lines tested (P <.05), enhanced radiosensitivity in all four cell lines, delayed DDR (P <.05), and increased proton vs photon RBE. Conclusion: Niraparib enhanced the sensitivity of four HNSCC cell lines to both photons and protons and increased the RBE of protons, possibly by inhibiting DDR. Niraparib may enhance the effectiveness of both photon and proton radiotherapy for patients with HNSCC.",

keywords = "PARP inhibitor, head and neck cancer, proton radiotherapy, radiosensitivity, relative biological effectiveness",

author = "Li Wang and Jianzhong Cao and Xiaochun Wang and Eric Lin and Zeming Wang and Yuting Li and Yupeng Li and Mei Chen and Xianliang Wang and Bo Jiang and Ruiping Zhang and Narayan Sahoo and Xiaodong Zhang and Zhu, {X. Ronald} and Myers, {Jeffrey N.} and Frank, {Steven J.}",

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T1 - Proton and photon radiosensitization effects of niraparib, a PARP-1/-2 inhibitor, on human head and neck cancer cells

AU - Wang, Li

AU - Cao, Jianzhong

AU - Wang, Xiaochun

AU - Lin, Eric

AU - Wang, Zeming

AU - Li, Yuting

AU - Li, Yupeng

AU - Chen, Mei

AU - Wang, Xianliang

AU - Jiang, Bo

AU - Zhang, Ruiping

AU - Sahoo, Narayan

AU - Zhang, Xiaodong

AU - Zhu, X. Ronald

AU - Myers, Jeffrey N.

AU - Frank, Steven J.

PY - 2020/9/1

Y1 - 2020/9/1

N2 - Background: Combining photon or proton radiotherapy with targeted therapy shows promise for head and neck cancer (HNSCC). The poly (adenosine diphosphate [ADP]-ribose) polymerase-1/2 inhibitor niraparib targets DNA damage repair (DDR). We evaluated the effects of niraparib in combination with photons or protons, and its effects on the relative biological effectiveness (RBE) of protons, in human HNSCC cell lines. Methods: Radiosensitivity was assessed and RBE was calculated with clonogenic survival assays; unrepaired DNA double-strand breaks were evaluated using immunocytochemical analysis of 53BP1 foci. Results: Niraparib reduced colony formation in two of the four cell lines tested (P <.05), enhanced radiosensitivity in all four cell lines, delayed DDR (P <.05), and increased proton vs photon RBE. Conclusion: Niraparib enhanced the sensitivity of four HNSCC cell lines to both photons and protons and increased the RBE of protons, possibly by inhibiting DDR. Niraparib may enhance the effectiveness of both photon and proton radiotherapy for patients with HNSCC.

AB - Background: Combining photon or proton radiotherapy with targeted therapy shows promise for head and neck cancer (HNSCC). The poly (adenosine diphosphate [ADP]-ribose) polymerase-1/2 inhibitor niraparib targets DNA damage repair (DDR). We evaluated the effects of niraparib in combination with photons or protons, and its effects on the relative biological effectiveness (RBE) of protons, in human HNSCC cell lines. Methods: Radiosensitivity was assessed and RBE was calculated with clonogenic survival assays; unrepaired DNA double-strand breaks were evaluated using immunocytochemical analysis of 53BP1 foci. Results: Niraparib reduced colony formation in two of the four cell lines tested (P <.05), enhanced radiosensitivity in all four cell lines, delayed DDR (P <.05), and increased proton vs photon RBE. Conclusion: Niraparib enhanced the sensitivity of four HNSCC cell lines to both photons and protons and increased the RBE of protons, possibly by inhibiting DDR. Niraparib may enhance the effectiveness of both photon and proton radiotherapy for patients with HNSCC.

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KW - proton radiotherapy

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KW - relative biological effectiveness

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Proton and photon radiosensitization effects of niraparib, a PARP-1/-2 inhibitor, on human head and neck cancer cells

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