The article "New light on chemotherapy toxicity and its prevention" by Ronit Juthani, Sachin Punatar, and Indraneel Mittra explores the emerging understanding of chemotoxicity and its prevention. Chemotherapy, while effective in treating cancer, often causes severe side effects due to systemic DNA damage and inflammation in healthy cells. Traditional views attributed these effects to direct cell death caused by chemotherapeutic drugs. However, recent research suggests that chemotoxicity is also influenced by the release of cell-free chromatin particles (cfChPs) from dying cells, which can enter and damage healthy cells, leading to a cascading effect of further cell death and inflammation. The article reviews laboratory studies, preclinical animal studies, and clinical trials that support this new understanding. Key findings include the role of cfChPs in the bystander effect, where dying cancer cells release cfChPs that integrate into the genomes of healthy cells, causing DNA damage and inflammation. Preclinical studies using cfChPs-deactivating agents, such as anti-histone antibody complexed nanoparticles (CNPs), DNase I, and the nutraceutical combination resveratrol and copper (R-Cu), have shown promising results in reducing chemotoxicity. These agents can deadenyze cfChPs, thereby minimizing their toxic effects. Clinical trials have further validated the potential of R-Cu in reducing chemotherapy-related toxicities, including mucositis, neutropenia, and non-hematological toxicities. Additionally, R-Cu has shown potential therapeutic effects on tumor cells by deactivating cfChPs in the tumor microenvironment, leading to the downregulation of cancer hallmarks and immune checkpoints. The article concludes by emphasizing the need for larger, well-designed clinical trials to confirm the clinical value of these findings and to further understand the mechanisms of chemotoxicity and its management. The authors highlight the potential of R-Cu as a potent cfChPs-deactivating agent and the importance of continued research to improve patient outcomes and quality of life.The article "New light on chemotherapy toxicity and its prevention" by Ronit Juthani, Sachin Punatar, and Indraneel Mittra explores the emerging understanding of chemotoxicity and its prevention. Chemotherapy, while effective in treating cancer, often causes severe side effects due to systemic DNA damage and inflammation in healthy cells. Traditional views attributed these effects to direct cell death caused by chemotherapeutic drugs. However, recent research suggests that chemotoxicity is also influenced by the release of cell-free chromatin particles (cfChPs) from dying cells, which can enter and damage healthy cells, leading to a cascading effect of further cell death and inflammation. The article reviews laboratory studies, preclinical animal studies, and clinical trials that support this new understanding. Key findings include the role of cfChPs in the bystander effect, where dying cancer cells release cfChPs that integrate into the genomes of healthy cells, causing DNA damage and inflammation. Preclinical studies using cfChPs-deactivating agents, such as anti-histone antibody complexed nanoparticles (CNPs), DNase I, and the nutraceutical combination resveratrol and copper (R-Cu), have shown promising results in reducing chemotoxicity. These agents can deadenyze cfChPs, thereby minimizing their toxic effects. Clinical trials have further validated the potential of R-Cu in reducing chemotherapy-related toxicities, including mucositis, neutropenia, and non-hematological toxicities. Additionally, R-Cu has shown potential therapeutic effects on tumor cells by deactivating cfChPs in the tumor microenvironment, leading to the downregulation of cancer hallmarks and immune checkpoints. The article concludes by emphasizing the need for larger, well-designed clinical trials to confirm the clinical value of these findings and to further understand the mechanisms of chemotoxicity and its management. The authors highlight the potential of R-Cu as a potent cfChPs-deactivating agent and the importance of continued research to improve patient outcomes and quality of life.