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

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.

journal_name

Genome Biol

journal_title

Genome biology

authors

Sa JK,Hwang JR,Cho YJ,Ryu JY,Choi JJ,Jeong SY,Kim J,Kim MS,Paik ES,Lee YY,Choi CH,Kim TJ,Kim BG,Bae DS,Lee Y,Her NG,Shin YJ,Cho HJ,Kim JY,Seo YJ,Koo H,Oh JW,Lee T,Kim HS,Song SY,Bae JS,Park WY,Han HD

doi

10.1186/s13059-019-1848-3

subject

Has Abstract

pub_date

2019-11-26 00:00:00

pages

253

issue

1

eissn

1474-7596

issn

1474-760X

pii

10.1186/s13059-019-1848-3

journal_volume

20

pub_type

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