Mechanisms of the FLASH effect: current insights and advances DOI Creative Commons
Giulia Rosini, Esther Ciarrocchi, Beatrice D’Orsi

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: May 9, 2025

Radiotherapy is a fundamental tool in cancer treatment, utilized over 60% of patients during their treatment course. While conventional radiotherapy effective, it has limitations, including prolonged durations, which extend patient discomfort, and toxicity to surrounding healthy tissues. FLASH (FLASH-RT), an innovative approach using ultra-high-dose-rate irradiation, shown potential selectively sparing normal tissues while maintaining unaltered tumor control. However, the precise mechanisms underlying this “FLASH effect” remain unclear. This mini-review explores key hypotheses, oxygen depletion, radical-radical interactions, mitochondrial preservation, differential DNA damage repair, immune modulation. Oxygen levels significantly affect tissue response radiation by promoting radical recombination, preserving function, differentially activating repair pathways versus extent depletion contributes effect remains debated. Additionally, FLASH-RT may modulate response, reducing inflammation cell function. To further enhance its therapeutic potential, increasingly being combined with complementary strategies such as radioprotectors, immunomodulators, nanotechnology platforms. These combinations aim amplify control toxicity, potentially overcoming current limitations. Despite promising preclinical evidence, exact clinical applicability require investigation. Addressing these gaps crucial for optimizing translating into improved outcomes patients. Continued research essential harness full benefits effect, offering paradigm shift oncology.

Language: Английский

Mechanisms of the FLASH effect: current insights and advances DOI Creative Commons
Giulia Rosini, Esther Ciarrocchi, Beatrice D’Orsi

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: May 9, 2025

Radiotherapy is a fundamental tool in cancer treatment, utilized over 60% of patients during their treatment course. While conventional radiotherapy effective, it has limitations, including prolonged durations, which extend patient discomfort, and toxicity to surrounding healthy tissues. FLASH (FLASH-RT), an innovative approach using ultra-high-dose-rate irradiation, shown potential selectively sparing normal tissues while maintaining unaltered tumor control. However, the precise mechanisms underlying this “FLASH effect” remain unclear. This mini-review explores key hypotheses, oxygen depletion, radical-radical interactions, mitochondrial preservation, differential DNA damage repair, immune modulation. Oxygen levels significantly affect tissue response radiation by promoting radical recombination, preserving function, differentially activating repair pathways versus extent depletion contributes effect remains debated. Additionally, FLASH-RT may modulate response, reducing inflammation cell function. To further enhance its therapeutic potential, increasingly being combined with complementary strategies such as radioprotectors, immunomodulators, nanotechnology platforms. These combinations aim amplify control toxicity, potentially overcoming current limitations. Despite promising preclinical evidence, exact clinical applicability require investigation. Addressing these gaps crucial for optimizing translating into improved outcomes patients. Continued research essential harness full benefits effect, offering paradigm shift oncology.

Language: Английский

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