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

Sarah Yoon, Eun Ju Lee, Ji Hye Choi, Taek Chung, doyoung kim, Jong Yeop Im, Myung Ho Bae, Jung Hee Kwon, Hyuk Hoon Kim, Hyung Chul Kim, Young Nyun Park, Hee Jung Wang, Hyun Goo Woo

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4443-4454
Number of pages12
JournalOncogene
Volume37
Issue number32
DOIs
Publication statusPublished - 2018 Aug 9

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Pharmacogenetics
Liver Neoplasms
Mutation
Precision Medicine
Therapeutics
Neoplasms
sorafenib
Pharmaceutical Preparations
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Yoon, Sarah ; Lee, Eun Ju ; Choi, Ji Hye ; Chung, Taek ; kim, doyoung ; Im, Jong Yeop ; Bae, Myung Ho ; Kwon, Jung Hee ; Kim, Hyuk Hoon ; Kim, Hyung Chul ; Park, Young Nyun ; Wang, Hee Jung ; Woo, Hyun Goo. / Recapitulation of pharmacogenomic data reveals that invalidation of SULF2 enhance sorafenib susceptibility in liver cancer. In: Oncogene. 2018 ; Vol. 37, No. 32. pp. 4443-4454.
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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.",
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Yoon, S, Lee, EJ, Choi, JH, Chung, T, kim, D, Im, JY, Bae, MH, Kwon, JH, Kim, HH, Kim, HC, Park, YN, Wang, HJ & Woo, HG 2018, 'Recapitulation of pharmacogenomic data reveals that invalidation of SULF2 enhance sorafenib susceptibility in liver cancer', Oncogene, vol. 37, no. 32, pp. 4443-4454. https://doi.org/10.1038/s41388-018-0291-3

Recapitulation of pharmacogenomic data reveals that invalidation of SULF2 enhance sorafenib susceptibility in liver cancer. / Yoon, Sarah; Lee, Eun Ju; Choi, Ji Hye; Chung, Taek; kim, doyoung; Im, Jong Yeop; Bae, Myung Ho; Kwon, Jung Hee; Kim, Hyuk Hoon; Kim, Hyung Chul; Park, Young Nyun; Wang, Hee Jung; Woo, Hyun Goo.

In: Oncogene, Vol. 37, No. 32, 09.08.2018, p. 4443-4454.

Research output: Contribution to journalArticle

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AU - Lee, Eun Ju

AU - Choi, Ji Hye

AU - Chung, Taek

AU - kim, doyoung

AU - Im, Jong Yeop

AU - Bae, Myung Ho

AU - Kwon, Jung Hee

AU - Kim, Hyuk Hoon

AU - Kim, Hyung Chul

AU - Park, Young Nyun

AU - Wang, Hee Jung

AU - Woo, Hyun Goo

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