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Recapitulation of pharmacogenomic data reveals that invalidation of SULF2 enhance sorafenib susceptibility in liver cancer

Authors
Yoon, S  | Lee, EJ | Choi, JH | Chung, T | Kim, DY | Im, JY | Bae, MH | Kwon, JH | Kim, HH  | Kim, HC | Park, YN | Wang, HJ  | Woo, HG
Citation
Oncogene, 37(32). : 4443-4454, 2018
Journal Title
Oncogene
ISSN
0950-92321476-5594
Abstract
Gene mutations play critical roles during cancer development and progression, and therefore represent targets for precision medicine. Here we recapitulated the pharmacogenomic data to delineate novel candidates for actionable mutations and therapeutic target drugs. As a proof-of-concept, we demonstrated that the loss-of-function of SULF2 by mutation (N491K) or inhibition enhanced sorafenib sensitivity in liver cancer cells and in vivo mouse models. This effect was mediated by deregulation of EGFR signaling and downstream expression of LCN2. We also report that the liver cancer patients non-responding to sorafenib treatment exhibit higher expression of SULF2 and LCN2. In conclusion, we suggest that SULF2 plays a key role in sorafenib susceptibility and resistance in liver cancer via deregulation of LCN2. Diagnostic or therapeutic targeting of SULF2 (e.g., OKN-007) and/or LCN2 can be a novel precision strategy for sorafenib treatment in cancer patients.
MeSH

DOI
10.1038/s41388-018-0291-3
PMID
29720727
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > School of Medicine / Graduate School of Medicine > Emergency Medicine
Journal Papers > School of Medicine / Graduate School of Medicine > Surgery
Ajou Authors
김, 혁훈  |  왕, 희정  |  우, 현구  |  윤, 사라
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