The new research by the scientists of Karolinska Institute and KI University Hospital reveals that radiotherapy (RT) results in epigenetic memory in the skin fibroblasts that hinders the healing of skin in cancer survivors. This study, published in Nature Communications, also demonstrates that this damage can be repaired by targeting specific antibodies at the memory site. This discovery can open further means of developing therapy for both the prevention of the appearance as well as treatment of RT-induced skin complications.
Radiotherapy (RT) can result in acute skin reactions as well as delayed toxicities such as ‘chronic ulcers and fibrosis,’ which may manifest after several years from treatment and seriously compromise the quality of life (QoL) of cancer survivors
Although it has been unknown as to why such long-term complications result from RT, the present study demonstrates that RT does generate epigenetic memory in skin fibroblasts, changing the manner they heal the wound. These thoughts throw key fibroblasts into overproduction of a protein known as THBS1, and the protein hampers the ability of fibroblasts to perform.
Remarkably, the researchers also revealed that binding these THBS1 with antibodies could solve the problem. The information outlined in this paper may contribute to the creation of new drugs that can be used in the prevention and treatment of skin complications arising from RT and thereby enhance the quality of life of many cancer survivors.
The researchers involved forty-six breast cancer survivors who had undergone radiotherapy in which the researchers took skin biopsies from treated and untreated regions during reconstructive surgeries.
Additionally, in more depth, they studied fibroblast activity and other chromatin modifications via ATAC-seq, RNA-seq, single-cell RNA-seq, and single-cell integrated ATAC-seq and RNA-seq.
The researchers also carried out some experiments whereby they exposed human ex vivo wound models to a topical treatment to see how it could improve the process through the abrogation of THBS1.
The next step is to explore anti-THBS1 antibodies and CD47 receptor inhibitors in clinical settings to assess their efficacy in controlling and eradicating skin reactions to radiotherapy in cancer survivors that develop later.
The researchers will assess the late outcomes of RT – they undertook a study, with breast cancer survivors receiving autologous-tissue breast reconstruction. Skin biopsies were taken specifically from the irradiated site (chest wall RT+) and other non-irradiated regions (usually the abdomen or a chest wall area opposite to the tumour site) during the reconstructive surgery. They also analyze epigenetic memory in other non-skeletal tissues and diseases to understand the general potential for using this process to prevent or treat diseases.
Reference: Bian X, Piipponen M, Liu Z, et al. Epigenetic memory of radiotherapy in dermal fibroblasts impairs wound repair capacity in cancer survivors. Nat Commun. 2024;15:9286. doi:10.1038/s41467-024-53295-1
