Abstract P4-06-13: Discovering serum biomarkers for predicting accumulation of nanotherapeutics to different tumor and organ microenvironments

Abstract

Abstract Surrogate biomarkers in the circulation for the enhanced permeation and retention (EPR) effect in different tumor and organ microenvironment shall aid in selecting patients who are likely to accumulate higher amount of nanotherapeutics to tumors and thus show better response to the therapeutics. In this study, 4T1 and 3LL murine cancer cell lines, known to have similar sensitivity to pegylated liposomal doxorubicin (PLD) in vitro, were shown to accumulate significantly different quantities of PLD in vivo. PLD accumulation correlated with tumor-specific differences in therapeutic efficacy and vascular permeability, which was modulated by the extent of coverage of tumor-associated endothelial cells by basement membrane. Matrix metalloproteinase (MMP)-9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1, played a pivotal role in these phenomena. Differences in vascular permeability and PLD accumulation were also organ-specific and significantly correlated with the relative ratio of MMP-9 and TIMP-1 in the systemic circulation of the tumor-bearing mice. Our findings support the further development of MMP-9 and TIMP-1 as paired serum biomarkers for predicting accumulation of PLD to tumor and the application of these biomarkers could be expanded to other types of nanotherapeutics utilizing the EPR effect for the personalization of cancer therapy. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-06-13.