Abstract
BACKGROUND: Bleomycin electrosclerotherapy (BEST) is an emerging treatment option for vascular malformations (VMs), predominantly slow-flow venous malformations, with increasing use in other types of VMs. By combining application of bleomycin with electroporation, BEST enhances intracellular drug delivery and may improve treatment efficacy while allowing the use of lower drug doses. Although clinical evidence supporting its efficacy is growing, the biological mechanisms underlying these effects remain poorly understood. Key unresolved questions include endothelial responses to BEST, what are the dominant mechanisms of vascular injury and remodeling, and how hemodynamics and abnormal vessel architecture affect bleomycin distribution, pharmacokinetics, and effective dosing within the lesion. Although the clinical effects of BEST may be similar to the vascular disrupting effect of electrochemotherapy, it remains unclear whether these vascular mechanisms are in fact the same. CONCLUSIONS: Understanding, how bleomycin is delivered, distributed, and retained within VM tissue, and how this interacts with endothelial susceptibility and electroporation efficiency, will be essential for defining optimal dosing strategies. Addressing these questions will require experimental approaches and physiologically relevant models capable of capturing the genetic, structural, and hemodynamic features of VMs. Such advances will be critical for elucidating the mechanisms of BEST and optimizing its clinical application.