||Translational Research in Carbon Ion Radiotherapy Focuses on Cancer Stem Cells
崔, 星 ,
鈴木, 雅雄 ,
小川, 幸大松本, 謙一郎
For the past twenty years, we have treated more than 10000 patients with various human cancer types by carbon ion radiotherapy and obtained promising outcomes. Here I want to show our recent new findings on the mechanisms of high radiocurability produced by carbon ion beams alone or in combination with some DNA damaging drugs from the point of view of targeting cancer stem cells (CSCs) in vitro and/or in vivo. We found that the relative biological effectiveness (RBE) values for the carbon ion beams relative to X-rays at the D10 levels for CSCs delivered from several cancer types such as colon cancer, pancreatic cancer, breast cancer were estimated around 2.1-2.4. Custom RT Profiler PCR Array analysis showed that expression of apoptosis- and autophagy-related genes such as BAX, Cytochrome c, LC3, p62 was significantly induced after carbon ion beam combined with gemcitabine or cisplatin compared to carbon ion beam alone. Xenograft tumors from pancreatic, triple negative (TN) breast cancer cells and malignant mesothelioma (MM) cells were effectively destroyed by 25 Gy of carbon ion beam combined with 50 mg/kg gemcitabine for pancreatic xenograft tumors or 15 Gy of carbon ion beam combined with 5 mg/kg cisplatin for TN breast cancer and MM xenograft tumors. Taken together, carbon ion beam has superior potential to kill pancreatic, TN breast and MM CSCs, and can achieve high curability when combined with DNA damaging drugs compared to carbon ion beam alone.
the 2th Symposium of the Medical Particle Beam Research Group