【Cell Discovery】Qin Wenxin's team at Shanghai Jiaotong University proposed a new treatment strategy for hepatocellular carcinoma: EGFR blockade combined with cabozantinib to improve clinical efficacy

This article is the original of translational medicine network, please indicate the source when reprinting

Author: Mia

Introduction: Liver cancer is the fourth most frequent cancer in China, and the fatality rate ranks second

Research background

 01 

Treatment options for patients with advanced hepatocellular carcinoma (HCC) are still limited

Since the approval of rigofenib in 2017, the list of second-line therapeutic candidates has been expanding in recent years, currently including rigofenib monotherapy, cabotinib, ramosumab or pemumab, and nilumab plus epitomumab in combination therapy

On August 23, Shanghai Jiao Tong University Qin Wenxin, René Bernards and Wang Cun joint newsletter published a research paper

team found that in mouse models of HCC caused by Met overexpression, caboztinib treatment produced a strong antitumor effect

The EGFR signaling pathway is associated with cabozantinib sensitivity

 02 

To solve this problem, the researchers treated a group of HCC cell lines with increased concentrations of

Therefore, the researchers identified compounds

In the group treated with cabozantinib, several independent gRNAs specifically reduced targeting EGFR, suggesting that EGFR inhibition was synthesized

EGFR blockade makes HCC sensitive

To verify whether the EGFR signaling pathway is associated with the limited response of cabozantinib, we established an EGFR knockout cell line

The synergistic effect of WZ3146 and afatinib with cabozantinib on SNU449 cells is significantly stronger than that of gefitinib

To elucidate the mechanism by which EGFR blockade and cabozantinib synergistically reduce HCC cell line viability, the researchers measured apoptosis induction

Preclinical model

 03 

To test whether the results of the in vitro study could be reproduced in a preclinical model, the researchers established two patient-derived HCC organoids for further analysis

Summary of the study

 04 

Cabozantinib combination therapy may have strong therapeutic potential

Resources:

This article is intended to introduce the progress of medical research and cannot be used as a reference for

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