Optimization of aminolevulinic acid-protoporphyrin IX for fluorescence-guided tumor resection and treatment

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NCI Diversity Supplement Application Parent grant: Optimization of aminolevulinic acid-protoporphyrin IX for fluorescence-guided tumor resection and treatment (R15CA268200-02, PI: Bin Chen) This diversity supplement application is to support Ms. Jordyn Olsen, a first-generation college graduate in her family, to pursue PhD training in cancer research with the goal of promoting women and minorities in cancer research workforce. Aminolevulinic acid (ALA) is one of a few FDA-approved intraoperative fluorescent probes and the only molecular probe based on the metabolic alterations in tumor cells. ALA has no fluorescence on its own and needs to be metabolized in the heme biosynthesis pathway in tumor cells to produce a fluorescent and photosensitizing metabolite protoporphyrin IX (PpIX), which enables tumor fluorescence imaging for tumor detection and photodynamic therapy (PDT) for cancer treatment. Although ALA-PpIX has been clinically used for fluorescence-guided tumor resection and cancer treatment, its applications are limited by low tumor PpIX fluorescence, high tumor fluorescence heterogeneity, and low tumor-to-normal tissue fluorescence contrast. Research supported by the parent grant has led to the identification of ABCG2 transporter activity as a critical factor in reducing tumor PpIX fluorescence. More importantly, we have identified clinically used agents to suppress ABCG2 activity to enhance tumor PpIX fluorescence. In this supplement research, Jordyn will determine whether variation in ABCG2 expression results in intra-tumor and inter-tumor heterogeneity in ALA- PpIX fluorescence. In addition, she will investigate whether PpIX fluorescence heterogeneity in tumor cells can be suppressed by ABCG2 inhibition. This proposed research is related to the on-going work supported by the parent grant funding and will further expand scope of parent grant research. Support from this supplement funding will enable Jordyn to complete the necessary training in cancer research so that she will have the knowledge and skills to start her career as a cancer researcher.