A therapeutic strategy for chemotherapy-resistant gastric cancer via destabilization of both β-catenin and ras

Won Ji Ryu, Jae Eun Lee, Yong Hee Cho, Gunho Lee, Mi Kyoung Seo, Sang Kyu Lee, Jeong Ha Hwang, Do Sik Min, Sung Hoon Noh, Soonmyung Paik, Sangwoo Kim, Jae Ho Cheong, Kang Yell Choi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Treatment of advanced gastric cancer patients with current standard chemotherapeutic agents frequently results in resistance, leading to poor overall survival. However, there has been no success in developing strategies to overcome it. We showed the expression levels of both β-catenin and RAS were significantly increased and correlated in tissues of 756 gastric cancer (GC) patients and tissues of primary- and acquired-resistance patient-derived xenograft tumors treated with 5- fluorouracil and oxaliplatin modulated with leucovorin (FOLFOX). On the basis of our previous studies, where small molecules to suppress colorectal cancer (CRC) via degrading both β-catenin and RAS were developed, we tested the effectiveness of KYA1797K, a representative compound functioning by binding axin, in the growth of GC cells. The efficacy test of the drugs using gastric tumor organoids of Apc1638N mice showed that the CD44 and ALDH1A3 cancer stem cell markers were induced by FOLFOX, but not by KYA1797K. KYA1797K also efficiently suppressed tumors generated by re-engrafting the FOLFOX-resistant patient-derived xenograft (PDX) tumors, which also showed resistance to paclitaxel. Overall, the small-molecule approach degrading both β-catenin and RAS has potential as a therapeutic strategy for treating GC patients resistant to current standard chemotherapies.

Original languageEnglish
Article number496
JournalCancers
Volume11
Issue number4
DOIs
Publication statusPublished - 2019 Apr

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'A therapeutic strategy for chemotherapy-resistant gastric cancer via destabilization of both β-catenin and ras'. Together they form a unique fingerprint.

  • Cite this

    Ryu, W. J., Lee, J. E., Cho, Y. H., Lee, G., Seo, M. K., Lee, S. K., Hwang, J. H., Min, D. S., Noh, S. H., Paik, S., Kim, S., Cheong, J. H., & Choi, K. Y. (2019). A therapeutic strategy for chemotherapy-resistant gastric cancer via destabilization of both β-catenin and ras. Cancers, 11(4), [496]. https://doi.org/10.3390/cancers11040496