Multiomic analysis identifies CPT1A as a potential therapeutic target in platinum-refractory, high-grade serous ovarian cancer

Resistance to platinum compounds is a major determinant of patient survival in high-grade serous ovarian cancer (HGSOC). To understand mechanisms of platinum resistance and identify potential therapeutic targets in resistant HGSOC, we generated a data resource composed of dynamic (±carboplatin) prot...

Ամբողջական նկարագրություն

Պահպանված է:
Մատենագիտական մանրամասներ
Հիմնական հեղինակներ: Dongqing Huang, Shrabanti Chowdhury, Hong Wang, Sara R. Savage, Richard G. Ivey, Jacob J. Kennedy, Jeffrey R. Whiteaker, Chenwei Lin, Xiaonan Hou, Ann L. Oberg, Melissa C. Larson, Najmeh Eskandari, Davide Delisi, Saverio Gentile, Catherine J. Huntoon, Uliana J. Voytovich, Zahra Shire, Qing Yu, Steven P. Gygi, Andrew N. Hoofnagle, Zachary T. Herbert, Travis D. Lorentzen, Anna Calinawan, Larry M. Karnitz, S. John Weroha, Scott H. Kaufmann, Bing Zhang, Pei Wang, Michael J. Birrer, Amanda G. Paulovich
Ձևաչափ: Artigo
Լեզու:անգլերեն
Հրապարակվել է: 2021
Առցանց հասանելիություն:https://doi.org/10.1016/j.xcrm.2021.100471
https://www.cell.com/article/S2666379121003438/pdf
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Նկարագրություն
Ամփոփում:Resistance to platinum compounds is a major determinant of patient survival in high-grade serous ovarian cancer (HGSOC). To understand mechanisms of platinum resistance and identify potential therapeutic targets in resistant HGSOC, we generated a data resource composed of dynamic (±carboplatin) protein, post-translational modification, and RNA sequencing (RNA-seq) profiles from intra-patient cell line pairs derived from 3 HGSOC patients before and after acquiring platinum resistance. These profiles reveal extensive responses to carboplatin that differ between sensitive and resistant cells. Higher fatty acid oxidation (FAO) pathway expression is associated with platinum resistance, and both pharmacologic inhibition and CRISPR knockout of