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Cited 17 time in webofscience Cited 17 time in scopus
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Pharmacogenomic analysis of patient-derived tumor cells in gynecologic cancersopen access

Authors
Sa, Jason K.Hwang, Jae RyoungCho, Young-JaeRyu, Ji-YoonChoi, Jung-JooJeong, Soo YoungKim, JihyeKim, Myeong SeonPaik, E. SunLee, Yoo-YoungChoi, Chel HunKim, Tae-JoongKim, Byoung-GieBae, Duk-SooLee, YeriHer, Nam-GuShin, Yong JaeCho, Hee JinKim, Ja YeonSeo, Yun JeeKoo, HarimOh, Jeong-WooLee, TaebumKim, Hyun-SooSong, Sang YongSeol, JoonPark, Woong-YangHan, Hee DongAhn, Hyung JunSood, Anil K.Rabadan, RaulLee, Jin-KuNam, Do-HyunLee, Jeong-Won
Issue Date
Nov-2019
Publisher
BioMed Central
Keywords
Gynecologic malignancy; Pharmacogenomic analysis; PARP inhibitor; TP53 mutations; ID2
Citation
Genome Biology, v.20, no.1
Indexed
SCI
SCIE
SCOPUS
Journal Title
Genome Biology
Volume
20
Number
1
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/1408
DOI
10.1186/s13059-019-1848-3
ISSN
1474-7596
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.
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College of Medicine (Department of Medical Informatics)
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