Pharmacogenomic analysis of patient-derived tumor cells in gynecologic cancers

Author:

Sa Jason K.,Hwang Jae Ryoung,Cho Young-Jae,Ryu Ji-Yoon,Choi Jung-Joo,Jeong Soo Young,Kim Jihye,Kim Myeong Seon,Paik E. Sun,Lee Yoo-Young,Choi Chel Hun,Kim Tae-Joong,Kim Byoung-Gie,Bae Duk-Soo,Lee Yeri,Her Nam-Gu,Shin Yong Jae,Cho Hee Jin,Kim Ja Yeon,Seo Yun Jee,Koo Harim,Oh Jeong-Woo,Lee Taebum,Kim Hyun-Soo,Song Sang Yong,Bae Joon Seol,Park Woong-Yang,Han Hee Dong,Ahn Hyung Jun,Sood Anil K.,Rabadan Raul,Lee Jin-KuORCID,Nam Do-Hyun,Lee Jeong-Won

Abstract

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.

Funder

Korea National Institute of Health

Publisher

Springer Science and Business Media LLC

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3