| 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 |
1 |
| 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 |
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| 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 |
| Attach file |
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| Citation |
0
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Publication
Journal Publication
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