NASHVILLE — Eben Rosenthal and Guolan Lu developed single-cell spatial pharmacobiology (SSP), a platform that visualizes drug-tumor interactions in human solid tumors, according to a study published in Nature Biotechnology in 2026. The study, titled “Single-cell spatial pharmacobiology identifies conserved stromal barriers to therapeutic antibody delivery in human solid tumors,” introduces SSP as a tool to measure drug delivery and signaling within tumors.
SSP enables researchers to examine how a drug distributes inside a tumor, which cell types it interacts with, how strongly it engages its molecular target, and how the architecture of the tumor microenvironment affects its delivery and activity. “SSP allows examination of how the drug distributes within the tumor, the cell types with which it interacts, how strongly it engages its molecular target, and how the architecture of the tumor microenvironment shapes its delivery and activity,” Rosenthal said.
Research using the platform revealed pronounced spatial heterogeneity—uneven physical distribution—in drug delivery and target engagement across different tumor types. Current pharmacological tools and imaging methods fall short in clarifying whether drugs fail because they cannot reach the tumor or because they lack sufficient activity once inside. “Current pharmacology tools and imaging methodologies do not provide the answers needed to understand which drugs fail due to poor delivery and which fail due to insufficient activity upon entering the tumor.”
The dense stromal architecture—the noncancerous tissue surrounding a tumor—acts as a physical barrier that blocks drugs from penetrating the tumor, according to Rosenthal. “The dense stromal architecture, or the noncancerous tissue surrounding a tumor, acts as a physical barrier to keep drugs out of the tumor.” By directly measuring drug delivery at the site of targeted antibody therapy, SSP can distinguish between tumor regions that are biologically unresponsive and those merely underexposed to the therapeutic agent. “By directly measuring drug delivery at the site of targeted antibody therapy, SSP can distinguish tumor regions that are biologically unresponsive from those that are simply underexposed to the agent.”
The research incorporated data from Phase 1 clinical trials using panitumumab-IRDye800CW, an antibody under investigation for fluorescence-guided surgery. Rosenthal, the Barry and Amy Baker Professor and Chair of the Department of Otolaryngology-Head and Neck Surgery at Vanderbilt Health, has focused on advancing fluorescence imaging in cancer research and surgery. Lu, of Stanford University School of Medicine, is a co-author of the paper. Additional validation in larger patient cohorts could further establish SSP’s utility in identifying barriers to drug efficacy, he noted. The work was supported by National Institutes of Health grants R01CA239257, R01CA266233, and R01CA279249.