Year: 2019
Type: article
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.
Source: Genome biology
Authors: Jason K. Sa, Jae Ryoung Hwang, Young-Jae Cho, Ji-Yoon Ryu, Jung-Joo Choi, Soo Young Jeong, Jihye Kim, Myeong Seon Kim, E. Sun Paik, Yoo-Young Lee, Chel Hun Choi, Tae-Joong Kim, Byoung-Gie Kim, Duk-Soo Bae, Yeri Lee, Nam-Gu Her, Yong Jae Shin, Hee Jin Cho, Ja Yeon Kim, Yun Jee Seo, Harim Koo, Jeong-Woo Oh, Taebum Lee, Hyun-Soo Kim, Sang Yong Song, Joon Seol Bae, Woong-Yang Park, Hee Dong Han, Hyung Jun Ahn, Anil K. Sood, Raul Rabadan, Jin-Ku Lee, Do-Hyun Nam, Jeong-Won Lee
Institutions: Korea University, Samsung Medical Center, Research Institute for Future Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University, Dankook University Hospital, Chonnam National University, Chonnam National University Hwasun Hospital, Konkuk University, Korea Institute of Science and Technology, The University of Texas MD Anderson Cancer Center, Columbia University, Ajou University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,490
OpenAlex ID: W2989869460