Establishment of photodynamic therapy with a novel photosensitizer for gemcitabine resistant pancreatic cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H07008
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Nagoya City University
• Principal Investigator: Kato Akihisa 名古屋市立大学, 大学院医学研究科, 臨床研究医 (10803489)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Keywords: 膵癌 / 光線力学療法 / PDT

Outline of Final Research Achievements

Photodynamic therapy (PDT) has gained considerable attention as an alternative to management of cancer. We synthesized oligosaccharide-conjugated chlorin (O-chlorin) to improve cancer selectivity as well as antitumor effect, and investigated its effect for Gemcitabine(GEM) resistant pancreatic cancer. After establishment of GEM resistant pancreatic cancer cell lines, we showed the cytotoxic effects were about 11 - 16 times higher than those of Talaporfin, which is clinically used. We additionally established experimental peritoneal disseminated xenograft mouse models of GEM resistant pancreatic cancer cells and demonstrated the high cancer selectivity of O-chlorin in in vivo model. However, O-chlorin PDT did not suppress tumor growth of peritoneal disseminated tumor in mice compared with the Talaporfin group. Therefore, further studies are needed to establish the usefulness of this novel PDT for GEM resistant pancreatic cancer.

Free Research Field

胆膵領域

Academic Significance and Societal Importance of the Research Achievements

我々は高い腫瘍細胞選択性を可能にしたオリゴ糖連結クロリンを開発し，次世代のPDTとして期待される．この技術はWarburg効果としてFDG-PET検査にも応用されているように，癌細胞に普遍的な糖の取り込みを応用しているので，新規糖鎖連結光感受性物質はほぼすべての癌に応用が可能であり，実臨床において問題となるGEM耐性の膵癌などに対しても非常に有用な抗癌治療法である．そこで本研究では，GEMが無効となり腹膜播種病変が出現した際，現在の医療では治療選択肢が何もない中で，積極的かつ低侵襲な腹膜播種巣に対する治療としての一つの治療選択を提案することを目的としている．