The contribution of high-LET track to DNA damage formation and cell death for Monoenergy and SOBP carbon ion irradiation

Chailapakul, Piyawan; Maloney, Olivia; Hirakawa, Hirokazu; Fujimori, Akira; Kitamura, Hisashi; Kato, Takamitsu A.

doi:10.1016/j.bbrc.2024.149500

Cited by 1 publication

(1 citation statement)

References 34 publications

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“…There is therefore a gradual increase in LET from the beam entrance towards the end of the Bragg peak. Clinical carbon ion beams produce high-LET radiation, with typical LET values within the spread-out Bragg peak (SOBP) of 40–80 keV/µm [ 4 ] and >200 keV/µm at the distal end [ 5 , 6 ], depending on the beam energy. For clinical proton beams, average LET values are approximately 2–3 keV/µm at the middle of the SOBP and 10–15 keV/µm at the distal end of the Bragg peak [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Potential Benefits of Combining Proton or Carbon Ion Therapy with DNA Damage Repair Inhibitors

Rødland,

Temelie,

Eek Mariampillai

et al. 2024

Cells

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The use of charged particle radiotherapy is currently increasing, but combination therapy with DNA repair inhibitors remains to be exploited in the clinic. The high-linear energy transfer (LET) radiation delivered by charged particles causes clustered DNA damage, which is particularly effective in destroying cancer cells. Whether the DNA damage response to this type of damage is different from that elicited in response to low-LET radiation, and if and how it can be targeted to increase treatment efficacy, is not fully understood. Although several preclinical studies have reported radiosensitizing effects when proton or carbon ion irradiation is combined with inhibitors of, e.g., PARP, ATR, ATM, or DNA-PKcs, further exploration is required to determine the most effective treatments. Here, we examine what is known about repair pathway choice in response to high- versus low-LET irradiation, and we discuss the effects of inhibitors of these pathways when combined with protons and carbon ions. Additionally, we explore the potential effects of DNA repair inhibitors on antitumor immune signaling upon proton and carbon ion irradiation. Due to the reduced effect on healthy tissue and better immune preservation, particle therapy may be particularly well suited for combination with DNA repair inhibitors.

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