ADAM10 Evens Out the Double-Edged Sword of Radiotherapy in Pancreatic Cancer

Abstract Radiotherapy plays an important role in the management of pancreatic ductal adenocarcinoma (PDAC), especially when patients are not surgical candidates. Radiation-induced tumor death provokes an acute inflammation followed by a late-fibrotic response that parallels the fibroinflammatory tumor microenvironment of PDAC, inciting the question of whether radiation-induced fibrosis contributes to PDAC progression. The study published in this issue by Mueller and colleagues presents a potential mechanism linking radiation-induced fibrosis with expression of a disintegrin and metalloprotease 10 (ADAM10) and ephrinB2, which may also contribute to tumor progression. The authors show that ablation of ADAM10 decreases radiation-induced fibrosis and improves survival in preclinical models. These data suggest that targeting ADAM10 may help to improve clinical outcomes with radiotherapy, particularly if definitive radiation is not possible. A better understanding of the biology of radiotherapy in pancreatic cancer remains crucial, and Mueller and colleagues offer important insight in this regard. See related article by Mueller et al., p. 3255