한빛사논문
- 조회3,037
Jason K. Sa1,2,3,†, Jae Ryoung Hwang4,†, Young-Jae Cho5,†, Ji-Yoon Ryu5, Jung-Joo Choi5, Soo Young Jeong5, Jihye Kim6, Myeong Seon Kim5, E. Sun Paik5, Yoo-Young Lee5, Chel Hun Choi5, Tae-Joong Kim5, Byoung-Gie Kim5, Duk-Soo Bae5, Yeri Lee1,2, Nam-Gu Her1,2, Yong Jae Shin1,2,7, Hee Jin Cho1,2, Ja Yeon Kim1,2, Yun Jee Seo1,2, Harim Koo1,8, Jeong-Woo Oh1,8, Taebum Lee9, Hyun-Soo Kim10, Sang Yong Song10, Joon Seol Bae11, Woong-Yang Park11, Hee Dong Han12, Hyung Jun Ahn13, Anil K. Sood14, Raul Rabadan15,16, Jin-Ku Lee17,*, Do-Hyun Nam1,7,8,* and Jeong-Won Lee1,5,8,*
1 Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Republic of Korea.
2 Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea.
3 Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea.
4 Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
5 Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
6 Department of Obstetrics and Gynecology, Dankook University Hospital, Cheonan, Republic of Korea.
7 Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
8 Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Republic of Korea.
9 Department of Pathology, Hwasun Hospital, Chonnam National University Medical School, Gwangju, Republic of Korea.
10 Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
11 Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea.
12 Department of Immunology, School of Medicine, Konkuk University, Chungju, Republic of Korea.
13 Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea.
14 Department of Gynecologic Oncology and Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
15 Department of Systems Biology, Columbia University, New York, NY, USA.
16 Department of Biomedical Informatics, Columbia University, New York, NY, USA.
17 Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon, Republic of Korea.
* Correspondence : Jin-Ku Lee, Do-Hyun Nam, Jeong-Won Lee
†Jason K. Sa, Jae Ryoung Hwang and Young-Jae Cho contributed equally to this work.
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
논문정보
- Research article
- 2019년 11월 (BRIC 등록일 2019-12-02)
- 국내(교신)+국외 연구진
- 의약학 > 종양의학
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