Wounding triggers invasive progression in human basal cell carcinoma

Summary: Abstract Body: The interconnection between wound healing and cancer has long been recognized, as epitomized by the expression “cancer is a wound that does not heal”. However, the impact of inducing a wound, such as through biopsy collection, on the progression of established tumors remains largely unknown. In this study, we apply spatial, single-cell transcriptomics to characterize the heterogeneity of human basal cell carcinoma (BCC) and identify a wound response-associated gene program as a prominent feature of invasive and therapy-resistant cancer cells. To explore the causal relationship between wounding and cancer progression, we compare human tumors at baseline and one week post-biopsy. Our results demonstrate that biopsy collection triggers, in proximity to the wound, a transcriptional switch in cancer cells and cancer-associated fibroblasts (CAFs) coupled with an invasive morphological pattern. Notably, the wound-induced cancer cell and CAF transcriptional states resemble those found in advanced, therapy-resistant BCC. This study provides evidence that wounding triggers invasive progression of established human tumors and warrants further research on the potentially harmful effects of biopsies and wound-inducing treatments. Laura Yerly¹, Massimo Andreatta², Josep Garnica², Charlée Nardin³, Jeremy Di Domizio¹, Francois Aubin³, Michel Gilliet¹, Santiago Carmona², Francois Kuonen¹ 1. Centre Hospitalier Universitaire Vaudois, Lausanne, VD, Switzerland. 2. Universite de Lausanne, Lausanne, VD, Switzerland. 3. Universite de Franche-Comte, Besançon, Bourgogne-Franche-Comté, France. UV Biology/Injury and Non-melanoma Cancers