Molecular Harvesting of Proteins with Electroporation In Vivo Facilitates the Profiling of Spatial Differential Protein Expression in Tumors

Abstract Background. Excision tissue biopsy, while central to cancer treatment and precision medicine, presents risks to the patient and does not provide a sufficiently broad and faithful representation of the heterogeneity of sampled solid tumors. Methods. Here we introduce e-biopsy – a novel concept for molecular profiling of solid tumors using molecular extraction with electroporation. As e-biopsy provides access to the molecular composition of a solid tumor, it potentially facilitates tumor diagnostics without tissue resection. Furthermore, thanks to its less invasive characteristics, e-biopsy enables probing the solid tumor multiple times in several distinct locations in the same procedure, thereby enabling the spatial profiling of tumor molecular heterogeneity.Results. We demonstrate e-biopsy in vivo, using the 4T1 breast cancer model in mice to assess its performance, as well as the inferred spatial differential protein expression. In particular, we show that proteomic profiles obtained via e-biopsy in vivo distinguish the tumors from healthy tissue and reflect spatial tumor differential protein expression.Conclusions. E-biopsy provides a completely new molecular cartography modality for solid tumors, providing information that potentially enables more sensitive detection, at lesser risk, as well as more precise personalized medicine.