성균관대학교 의과대학, 삼성서울병원

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Pharmacogenomic analysis of patient-derived tumor cells in gynecologic cancers
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Abstract

Background
Gynecologic malignancy is one of the leading causes of mortality in female adults worldwide. Comprehensive genomic analysis has revealed a list of molecular aberrations that are essential to tumorigenesis, progression, and metastasis of gynecologic tumors. However, targeting such alterations has frequently led to treatment failures due to underlying genomic complexity and simultaneous activation of various tumor cell survival pathway molecules. A compilation of molecular characterization of tumors with pharmacological drug response is the next step toward clinical application of patient-tailored treatment regimens.

Results
Toward this goal, we establish a library of 139 gynecologic tumors including epithelial ovarian cancers (EOCs), cervical, endometrial tumors, and uterine sarcomas that are genomically and/or pharmacologically annotated and explore dynamic pharmacogenomic associations against 37 molecularly targeted drugs. We discover lineage-specific drug sensitivities based on subcategorization of gynecologic tumors and identify TP53 mutation as a molecular determinant that elicits therapeutic response to poly (ADP-Ribose) polymerase (PARP) inhibitor. We further identify transcriptome expression of inhibitor of DNA biding 2 (ID2) as a potential predictive biomarker for treatment response to olaparib.

Conclusions
Together, our results demonstrate the potential utility of rapid drug screening combined with genomic profiling for precision treatment of gynecologic cancers.

Keywords: Gynecologic malignancy, Pharmacogenomic analysis, PARP inhibitor, TP53 mutations, ID2

주소복사
논문정보   
- 형식: Research article
- 게재일: 2019년 11월 (BRIC 등록일 2019-11-27)
- 연구진: 국내(교신)+국외 연구진태극기
- 분야: Biotechnology, Genetics
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