Related Experiment Video

Updated: Jul 20, 2025

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
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An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

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Autophagy and biotransformation affect sorafenib resistance in hepatocellular carcinoma

Ruiqi Zheng1, Shuang Weng2, Jianping Xu3

  • 1State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Computational and Structural Biotechnology Journal
|July 31, 2023
PubMed

Insights

Pretreatment factors like PI3K/AKT activation, biotransformation, and autophagy influence hepatocellular carcinoma (HCC) patient response to sorafenib. Key molecules ADH1A and STING1 are implicated in sorafenib resistance, suggesting new therapeutic targets.

Area of Science:

  • Oncology
  • Proteomics
  • Molecular Biology

Background:

  • Sorafenib is a primary treatment for advanced hepatocellular carcinoma (HCC).
  • Sorafenib resistance is a significant clinical challenge, with most research focusing on post-treatment resistance mechanisms.
  • Understanding pretreatment factors influencing sorafenib sensitivity is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate potential pretreatment factors that affect sorafenib resistance in hepatocellular carcinoma using proteomic techniques.
  • To identify key molecular players involved in the development of sorafenib resistance prior to treatment initiation.

Main Methods:

  • Proteomic analysis of hepatocellular carcinoma patient samples.
  • Investigation of pathway activation (PI3K/AKT), biotransformation capacity, and autophagy levels.
  • Identification of key molecules such as ADH1A and STING1.

Main Results:

  • Pretreatment PI3K/AKT pathway activation, biotransformation capacity, and autophagy levels are associated with sorafenib resistance in HCC.
  • ADH1A and STING1 were identified as key molecules influencing sorafenib sensitivity.
  • These factors interact to promote tumor cell survival and are linked to HCC prognosis.

Conclusions:

  • Pretreatment cellular states, including PI3K/AKT activation, biotransformation, and autophagy, significantly impact sorafenib efficacy in HCC.
  • Targeting ADH1A and STING1 may offer novel therapeutic strategies for overcoming sorafenib resistance.
  • Findings suggest potential for immunotherapy in improving survival for sorafenib-resistant HCC patients.
Keywords:
AutophagyBiotransformationHCCPI3K/AKT/mTORProteomicsSorafenib resistance

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