Document Type
Article
Publication Date
9-1-2024
Abstract
AIMS: Resistance to targeted therapy is one of the critical obstacles in cancer management. Resistance to trastuzumab frequently develops in the treatment for HER2
METHODS: Four public datasets were used to screen PTP candidates in relation to trastuzumab responsiveness in HER2
RESULTS: PTPRO was identified as the key PTP which influences trastuzumab responsiveness and patient survival. PTPRO de-phosphorated several TKs, including the previously overlooked substrate ERBB3, thereby inhibiting multiple oncogenic pathways associated with drug resistance. Notably, PTPRO, previously deemed "undruggable," was effectively upregulated by saRNA-loaded nanoparticles. The upregulated PTPRO simultaneously inhibited ERBB3, ERBB2, and downstream SRC signaling pathways, thereby counteracting trastuzumab resistance.
CONCLUSIONS: Antibody-conjugated saRNA represents an innovative approach for targeting "undruggable" PTPs.
Publication Title
Drug Resistance Updates
Volume
76
PubMed ID
39094301
Recommended Citation
Wang, Lu; Lin, Yusheng; Yao, Zhimeng; Babu, Nipun; Lin, Wan; Chen, Chaoying; Du, Liang; Cai, Songwang; Pan, Yunlong; Xiong, Xiao; Ye, Qiantao; Ren, Hongzheng; Zhang, Dianzheng; Chen, Yexi; Yeung, Sai-Ching Jim; Bremer, Edwin; and Zhang, Hao, "Targeting undruggable phosphatase overcomes trastuzumab resistance by inhibiting multi-oncogenic kinases." (2024). PCOM Scholarly Works. 2275.
https://digitalcommons.pcom.edu/scholarly_papers/2275
DOI: https://doi.org/10.1016/j.drup.2024.101118
Comments
This article was published in Drug Resistance Updates, Volume 76.
The published version is available at https://doi.org/10.1016/j.drup.2024.101118.
Copyright © 2024 The Author(s). CC BY-NC-ND 4.0.