Eben Rosenthal, MD, the Barry and Amy Baker Professor and Chair of the Department of Otolaryngology-Head and Neck Surgery at Vanderbilt Health, is the senior author of the paper. Rosenthal and co-author Guolan Lu, PhD, of Stanford University School of Medicine, developed single-cell spatial pharmacobiology (SSP), an experimental and analytical platform that allows visualization of drug-tumor interactions in human solid tumors. SSP is a new tool for measuring drug delivery and signaling in the tumor.
"Identifying the reason drugs fail in so many cancer patients is a high priority, and SSP can help," said Rosenthal. "Current pharmacology tools and imaging methodologies do not provide the answers we need to understand which drugs fail due to poor delivery and which ones fail due to insufficient activity upon entering the tumor."
Research using SSP revealed that there was pronounced spatial heterogeneity, or uneven physical distribution, in drug delivery and target engagement across different tumor types. Rosenthal said this indicates that the dense stromal architecture, or the noncancerous tissue surrounding a tumor, acts as a physical barrier to keep drugs out of the tumor.
"This approach allows us to examine 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 added.
Panitumumab-IRDye800CW, a drug used in Phase 1 clinical trials that were considered in SSP research, is an antibody under investigation for application in fluorescence-guided surgery. Rosenthal has helped navigate his department along the cutting edge of fluorescence imaging in cancer research, treatment and surgery.
"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," said Rosenthal. "We hope additional study in larger sample sizes of patients can help further validate the application of SSP to identify barriers to drug efficacy."
This research was supported by National Institutes of Health grants R01CA239257, R01CA266233 and R01CA279249.
