1. BNCT pancreatic cancer treatment strategy with glucose-conjugated boron drug.
- Author
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Fujimoto T, Teraishi F, Kanehira N, Tajima T, Sakurai Y, Kondo N, Yamagami M, Kuwada A, Morihara A, Kitamatsu M, Fujimura A, Suzuki M, Takaguchi Y, Shigeyasu K, Fujiwara T, and Michiue H
- Subjects
- Humans, Cell Line, Tumor, Animals, Boron Compounds chemistry, Boron Compounds therapeutic use, Boron chemistry, Female, Mice, Nude, Boron Neutron Capture Therapy methods, Pancreatic Neoplasms therapy, Pancreatic Neoplasms pathology, Glucose metabolism
- Abstract
Multidisciplinary therapy centered on radical surgery for resectable pancreatic cancer is expected to prolong prognosis, but relies on CA19-9 biomarker levels to determine treatment strategy. Boron neutron capture therapy (BNCT) is a chemoradiotherapy using tumor hyperaccumulator boron drugs and neutron irradiation. The purpose of this study is to investigate novel boron drug agents for BNCT for pancreatic cancer. Bioinformatics was used to evaluate the uptake of current boron amino acid (BPA) drugs for BNCT into pancreatic cancer. The expression of the amino acid transporter LAT1, a BPA uptake transporter, was low in pancreatic cancer and even lower in high CA19-9 pancreatic cancer. In contrast, the glucose transporter was high in high CA19-9 pancreatic cancers and inversely correlated with LAT1 expression. Considering the low EPR effect in pancreatic cancer, we synthesized a small molecule Glucose-BSH, which is boron BSH bound to glucose, and confirmed its specific uptake in pancreatic cancer. uptake of Glucose-BSH was confirmed in an environment compatible with the tumor microenvironment. The therapeutic efficacy and safety of Glucose-BSH by therapeutic neutron irradiation were confirmed with BNCT. We report Glucose-BSH boron drug discovery study of a Precision Medicine BNCT with application to high CA19-9 pancreatic cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All of author have no C.O.I., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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