Pharmacogenomic analysis of patient-derived tumor cells in gynecologic cancers

Title
Pharmacogenomic analysis of patient-derived tumor cells in gynecologic cancers
Authors
안형준사 제이슨황재령조영재류지윤최정주정수영김지혜김명선백은선이유영최철헌김태중김병기배덕수이예리허남구신용재조희진김자연서윤지구하림오정우이태범김현수송상용배준설박웅양한희동아닐 수드라울 라바단이진구남도현이정원
Keywords
ovarian cancer; pharmacogenomic analysis; patient-derived tumor cell; anticancer effect; drug response
Issue Date
2019-12
Publisher
Genome Biology
Citation
VOL 20, NO 253-13
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.
URI
http://pubs.kist.re.kr/handle/201004/72303
ISSN
1474-760X
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KIST Publication > Article
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