2012 ©
             Publication
Journal Publication
Research Title Synthetic lethal therapy in DNA damage repair-deficient cells: Therapeutic strategy for cholangiocarcinoma 
Date of Distribution 22 September 2023 
Conference
     Title of the Conference Welcome to the New Era 
     Organiser The Japan Cancer Association 
     Conference Place Pacifico Yokohama 
     Province/State Japan 
     Conference Date 21 September 2023 
     To 23 September 2023 
Proceeding Paper
     Volume 82 
     Issue
     Page 907 
     Editors/edition/publisher The Japan Cancer Association 
     Abstract The defects of DNA-damage repair (DDR) genes are contributed to the carcinogenesis of cholangiocarcinoma (CCA). DDR-deficient tumors are more sensitive to DDR inhibitors (DDRi) through synthetic lethality mechanisms. This study evaluates the antitumor effect of DDRi (olaparib, niraparib, and AZD0156) on CCA cells harboring DDR mutations. DDR gene alterations were analyzed on CCA samples using the cBioPortal database. Screening of DDR gene mutation in 11 CCA cell lines was analyzed by whole exome sequencing (WES). The cBioPortal showed that at least one DDR mutation was detected in 35.8% of CCA cases, suggesting their susceptibility to DDRi. The most frequently mutated genes by WES analysis were BRCA2, CHEK1, FANCA, and ATR. For the drug sensitivity testing, KKU-023 and KKU-100 showed the highest sensitivity to AZD0156. In addition, KKU-023 showed the highest sensitivity to olaparib and niraparib. Furthermore, the DDRi combination showed a synergistic effect to suppress CCA cell growth and induced apoptosis approximately 15 times higher than the single treatment groups. In summary, combining DDRi regimens can be utilized for synthetic lethal therapy in CCA harboring DDR mutations. [Disclosure of COI by Responsible researcher] Lead presenter is the Responsible researcher. [Lead presenter] We have no financial relationships to disclose.] We have no financial relationships to disclose. 
Author
657070001-5 Miss RATTANAPORN JAIDEE [Main Author]
Medicine Doctoral Degree

Peer Review Status มีผู้ประเมินอิสระ 
Level of Conference นานาชาติ 
Type of Proceeding Abstract 
Type of Presentation Poster 
Part of thesis true 
Presentation awarding true 
     Award Title Travel grant award 
     Type of award รางวัลด้านวิชาการ วิชาชีพ 
     Organiser The Japan Cancer Association 
     Date of awarding 22 กันยายน 2566 
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