Abstract

Abstract Photodynamic therapy (PDT) involves the combination of a photosensitizer and light of a specific wavelength. Upon light activation in the presence of oxygen, photosensitizer molecules generate reactive oxygen species that cause cytotoxicity by inducing oxidative stress. Aminolevulinic acid (ALA) is a pro-drug used for the diagnosis and PDT treatment of various solid tumors based on endogenous production of heme precursor protoporphyrin IX (PpIX). Although all human cells express heme biosynthesis enzymes and produce PpIX, tumor cells are often found to have higher PpIX production and accumulation than normal cells, allowing for the detection and treatment of solid tumors. In exploring ALA-based tumor detection and therapy in breast cancer, we have reported that high ABCG2 transporter activity in triple negative breast cancer cells (TNBC) contributes to reduced PpIX levels in tumor cells, causing cell resistance to ALA-PDT. The administration of an ABCG2 inhibitor Ko143 was able to reverse cell resistance to ALA-PDT by increasing PpIX levels. In this study, we showed that some kinase inhibitors were able to increase ALA-mediated PpIX by inhibiting ABCG2 activity. Particularly, our results demonstrate that lapatinib, a dual inhibitor of EGFR and Her2, increased the ALA-PpIX level and cell sensitivity to ALA-PDT in the MDA-MB-231 TNBC cells. Lapatinib treatment had little effect on MCF10A breast epithelial cells. These results indicate that small molecule kinase inhibitors such as lapatinib can be used for enhancing ALA-based tumor detection and PDT in tumors with high ABCG2 activity. Citation Format: Bin Chen, Pratheeba Palasuberniam. Therapeutic enhancement of aminolevulinic acid-mediate tumor fluorescence and photodynamic therapy with kinase inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5842. doi:10.1158/1538-7445.AM2017-5842

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