From Genotoxic Stresses to Skin Damage: Distinct, Novel Mechanisms of Skin and Hair Damage in Chemo/Radiation Therapy

The document presents findings on the mechanisms of skin and hair damage caused by genotoxic stresses such as ionizing radiation (IR) and chemotherapy. The study conducted by Yue's laboratory revealed several key discoveries: (1) Chemotherapy-induced tissue damage in hair and feather follicles is marked by a critical early event of down-regulation of sonic hedgehog (Shh) gene expression. (2) IR-induced skin damage, a common side effect in cancer radiotherapy, involves significant changes in keratin gene expression, particularly Keratin 17, leading to the disruption of the cytoskeleton and adherens junctions in the epidermis, which in turn activates Wnt and Hippo signaling pathways, causing compensatory cell proliferation and desquamation. (3) The hair follicle serves as a model to investigate the synergistic damage caused by chemotherapy drugs like 5-flurouracil and taxol when combined with IR. These findings offer insights into the molecular mechanisms of skin and hair damage during cancer therapy and may help in testing new chemicals to enhance therapy efficacy.