Radiosensitization by PARP inhibition to proton beam irradiation in cancer cells

Hirai, Takahisa; Saito, Soichiro; Fujimori, Hiroaki; Matsushita, K.; Nishio, Teiji; Okayasu, Ryuichi; Masutani, Mitsuko

doi:10.1016/j.bbrc.2016.07.062

Cited by 38 publications

(36 citation statements)

References 21 publications

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“…High LET protons are known to cause complicated DNA damage, which is difficult to repair; its repair depends on DDR-related proteins, including expression and activity of PARP1, to ensure subsequent cell survival. 43,57 PARP inhibitors are thus thought to have promise in improving the response of a variety of tumors to proton therapy, 42,43 but whether PARP inhibitors can modulate the response of HNSCC cells to protons is unknown. Here, we present the first evidence that the PARP inhibitor niraparib significantly enhanced the responsiveness of all four HNSCC cell lines to PRT, which in turn suggests that the combination of niraparib and PRT may have clinical benefits in terms of improving tumor control for patients with both HPV+ and HPV− HNSCC.…”

Section: Discussionmentioning

confidence: 99%

“…41 However, investigations of this potential effect are in their infancy. As one example, the PARP inhibitor olaparib has been found to enhance the responsiveness of human lung cancer cells (A549), human pancreatic cancer cells (MIA PaCa-2), 42 and HPV− HNSCC cells (UMSCC74A) to PRT. 43 However, whether other PARP inhibitors, such as niraparib, can radiosensitize HNSCC cells or enhance tumor cell death in animal models in response to either XRT or PRT is unknown.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…Due to the moderate integral dose that is delivered to self-renewing surrounding normal tissues (e.g., skin, digestive tract), with particle irradiation modalities [153][154][155], the toxicity of the combination is expected to be lower. Furthermore, the radiosensitizing effects are higher in extent in the Bragg peak than in the entrance region [156], which allows the therapeutic ratio of PARPi as a radiosensitizer to be increased. Finally, high-LET irradiation induces more complex DNA damage than photons-particularly, oxidative clustered DNA lesions that comprise oxidized bases, apurinic-apyrimidinic sites, and SSBs.…”

Section: Parp Inhibitors In Association With Radiotherapymentioning

confidence: 99%

Hadrontherapy Interactions in Molecular and Cellular Biology

Thariat

Valable

Laurent

et al. 2019

IJMS

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The resistance of cancer cells to radiotherapy is a major issue in the curative treatment of cancer patients. This resistance can be intrinsic or acquired after irradiation and has various definitions, depending on the endpoint that is chosen in assessing the response to radiation. This phenomenon might be strengthened by the radiosensitivity of surrounding healthy tissues. Sensitive organs near the tumor that is to be treated can be affected by direct irradiation or experience nontargeted reactions, leading to early or late effects that disrupt the quality of life of patients. For several decades, new modalities of irradiation that involve accelerated particles have been available, such as proton therapy and carbon therapy, raising the possibility of specifically targeting the tumor volume. The goal of this review is to examine the up-to-date radiobiological and clinical aspects of hadrontherapy, a discipline that is maturing, with promising applications. We first describe the physical and biological advantages of particles and their application in cancer treatment. The contribution of the microenvironment and surrounding healthy tissues to tumor radioresistance is then discussed, in relation to imaging and accurate visualization of potentially resistant hypoxic areas using dedicated markers, to identify patients and tumors that could benefit from hadrontherapy over conventional irradiation. Finally, we consider combined treatment strategies to improve the particle therapy of radioresistant cancers.

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“…Therefore, PARP-1 inhibition can be a potential strategy to enhance efficacy of heavy ion radiation therapy. Finally, AZD2281 (Olaparib), a well-known PARP-1 inhibitor, was found to sensitize cancer cells to carbon ion and proton irradiation through delayed DNA repair process and cell cycle arrest [29,30].…”

Section: Poly(adp-ribose) Polymerase Inhibitorsmentioning

confidence: 99%

Strategies to Enhance Radiosensitivity to Heavy Ion Radiation Therapy

Lee

Okayasu

2018

International Journal of Particle Therapy

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Heavy ion radiation therapy has been increasingly used due to several advantages over low linear energy transfer (LET) photon therapy, but further improvement of its therapeutic efficacy would be necessary. In this review, we summarize effective radiosensitizers for heavy ion radiation therapy and mechanisms associated with the radiosensitization. High LET heavy ions induce more complex and clustered DNA damage than low LET radiation. Inhibition of homologous recombimation repair or nonhomologous end rejoining and dysfunctional cell cycle checkpoint have been reported to sensitize cancer cells to heavy ions. Radiosenstizing agents, including DNA damage response inhibitors, Hsp90 inhibitors, histone acetylase inhibitors, and nanomaterials have been found to enhance cell killing by heavy ion irradiation through disrupted DNA damage response, cell cycle arrest, or other cellular processes. The use of these radiosensitizers could be a promising strategy to enhance the efficacy of heavy ion radiation therapy.

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Radiosensitization by PARP inhibition to proton beam irradiation in cancer cells

Cited by 38 publications

References 21 publications

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

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

Hadrontherapy Interactions in Molecular and Cellular Biology

Strategies to Enhance Radiosensitivity to Heavy Ion Radiation Therapy

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