Mechanisms of Action in FLASH Radiotherapy: A Comprehensive Review of Physicochemical and Biological Processes on Cancerous and Normal Cells

• Published in: Cells (Basel, Switzerland) Vol. 13; no. 10; p. 835
• Main Authors: Chow, James C L, Ruda, Harry E
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.05.2024
• Subjects: Animals; Biology; Biophysics; Blood vessels; Cancer; cancer cell kill; Cancer therapies; Care and treatment; cell function; Cells; FLASH; Gastrointestinal system; Gastrointestinal tract; Humans; Immune response; Immunotherapy; Ion beams; Molecular biology; Neoplasms - metabolism; Neoplasms - pathology; Neoplasms - radiotherapy; normal cell sparing; Oxygen depletion; Radiation therapy; Radiotherapy; Radiotherapy - methods; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reviews; Skin; Toxicity; Tumor microenvironment; Tumor Microenvironment - radiation effects; Tumors; ultra-high dose rate; Canada; cell function; cancer cell kill; preclinical model; ultra-high dose rate; oxygen depletion; physicochemical process; radiotherapy; biological process; FLASH; normal cell sparing
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells13100835

The advent of FLASH radiotherapy (FLASH-RT) has brought forth a paradigm shift in cancer treatment, showcasing remarkable normal cell sparing effects with ultra-high dose rates (>40 Gy/s). This review delves into the multifaceted mechanisms underpinning the efficacy of FLASH effect, examining both physicochemical and biological hypotheses in cell biophysics. The physicochemical process encompasses oxygen depletion, reactive oxygen species, and free radical recombination. In parallel, the biological process explores the FLASH effect on the immune system and on blood vessels in treatment sites such as the brain, lung, gastrointestinal tract, skin, and subcutaneous tissue. This review investigated the selective targeting of cancer cells and the modulation of the tumor microenvironment through FLASH-RT. Examining these mechanisms, we explore the implications and challenges of integrating FLASH-RT into cancer treatment. The potential to spare normal cells, boost the immune response, and modify the tumor vasculature offers new therapeutic strategies. Despite progress in understanding FLASH-RT, this review highlights knowledge gaps, emphasizing the need for further research to optimize its clinical applications. The synthesis of physicochemical and biological insights serves as a comprehensive resource for cell biology, molecular biology, and biophysics researchers and clinicians navigating the evolution of FLASH-RT in cancer therapy.