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Updated: Dec 31, 2025

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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Over-expression of EGFR regulated by RARA contributes to 5-FU resistance in colon cancer

Xin-Yue Gu1, Yang Jiang2, Ming-Qi Li1

  • 1Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150040, People's Republic of China.

Aging
|January 4, 2020
PubMed

Insights

Targeting autophagy genes is a new cancer therapy strategy. This study identified key interactions between autophagy and clinically actionable genes, like EGFR and RARA, revealing their role in patient survival and drug resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Targeting the autophagic pathway presents a promising strategy for cancer therapy.
  • Comprehensive characterization of autophagy genes and their clinical relevance in cancer is currently lacking.
  • Understanding these genes is crucial for developing effective cancer treatments.

Purpose of the Study:

  • To systematically characterize alterations in autophagy genes across multiple cancer types.
  • To identify interactions between autophagy genes and clinically actionable genes (CAGs).
  • To investigate the clinical relevance of autophagy gene alterations and their impact on patient survival and drug resistance.

Main Methods:

  • Analysis of The Cancer Genome Atlas and CellMiner databases for autophagy gene alterations.
  • Identification of gene interactions using co-expression, protein-protein interactions (PPIs), and transcription factor (TF) data.
  • In vivo and in vitro validation of EGFR's role in 5-FU resistance in colon cancer cells.

Main Results:

  • A key subnetwork of 18 autophagy genes and 22 CAGs was identified, including EGFR targeted by RARA.
  • Alterations in autophagy gene expression were associated with patient survival across multiple cancer types.
  • EGFR was found to induce 5-FU resistance in colon cancer cells via autophagy, with RARA regulating EGFR overexpression.

Conclusions:

  • This study provides a comprehensive analysis of autophagy gene alterations in various cancer cell lines.
  • The findings highlight the potential clinical utility of targeting specific autophagy genes, such as EGFR and RARA, in cancer therapy.
  • Targeting the RARA-EGFR axis may overcome 5-FU resistance in colorectal cancer.
Keywords:
5-fluorouracilEGFRautophagydrug sensitivity

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