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Tumor Biology

, Volume 35, Issue 12, pp 11701–11709 | Cite as

EGFR inhibitors and autophagy in cancer treatment

  • Jie Cui
  • Yun-Feng Hu
  • Xie-Min Feng
  • Tao Tian
  • Ya-Huan Guo
  • Jun-Wei Ma
  • Ke-Jun Nan
  • Hong-Yi Zhang
Review

Abstract

Epidermal growth factor receptor (EGFR) inhibitor treatment is a strategy for cancer therapy. However, innate and acquired resistance is a major obstacle of the efficacy. Autophagy is a self-digesting process in cells, which is considered to be associated with anti-cancer drug resistance. The activation of EGFR can regulate autophagy through multiple signal pathways. EGFR inhibitors can induce autophagy, but the specific function of the induction of autophagy by EGFR inhibitors remains biphasic. On the one hand, autophagy induced by EGFR inhibitors acts as a cytoprotective response in cancer cells, and autophagy inhibitors can enhance the cytotoxic effects of EGFR inhibitors. On the other hand, a high level of autophagy after treatment of EGFR inhibitors can also result in autophagic cell death lacking features of apoptosis, and the combination of EGFR inhibitors with an autophagy inducer might be beneficial. Thus, autophagy regulation represents a promising approach for improving the efficacy of EGFR inhibitors in the treatment of cancer patients.

Keywords

EGFR-TKI Gefitinib Erlotinib Cetuximab EGFR Autophagy Resistance 

Abbreviations

ATG

Autophagy-related genes

PI3K-III

Class III phosphatidylinositol-3 kinase

PI3K-I

Class I phosphoinositide 3-kinase

Vps34

Vesicular protein sorting 34

EGFR

Epidermal growth factor receptor

BNIP3

Bcl-2/adenovirus E1B 19-kDa interacting protein 3

LC3

Cytosolic microtubule-associated protein light chain 3

AMPK

AMP-activated protein kinase

MAPK

Mitogen-activated protein kinase

ERK

Extracellular signal-related kinase

RTKs

Receptor tyrosine kinases

TSC2

Tuberous sclerosis protein 2

SGLT1

Sodium/glucose cotransporter 1

S6K1

S6 kinase 1

4EBP1

4E-binding protein 1

EGFR-TKIs

EGFR tyrosine kinases

NSCLC

Non-small cell lung cancer

SCLC

Small cell lung cancer

CQ

Chloroquine

HCQ

Hydroxychloroquine

ER

Erlotinib resistant

GR

Gefitinib resistant

AVO

Acidic vesicular organelle

DRAM1

Damage-regulated autophagy modulator 1

NOX4

NADPH oxidase 4

PTEN

Phosphatase with tensin homologue

HIF1-α

Hypoxia-inducible factor 1-α

ACRC

Advanced colorectal cancer

PFS

Progress-free survival

ORR

Objective response rate

Notes

Acknowledgments

We would like to offer special thanks to the Department of Oncology, Yanan University Affiliated Hospital, and the Center of Molecular Biology of Xi’an Jiaotong University for their help with the manuscript. The study is supported by the national specialised research fund for the doctor degree program of institute (Grant No 20110201120061) and the National Science Foundation for Young Scholars of China (Grant No 81301909).

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Jie Cui
    • 1
    • 2
  • Yun-Feng Hu
    • 2
  • Xie-Min Feng
    • 2
  • Tao Tian
    • 1
  • Ya-Huan Guo
    • 4
  • Jun-Wei Ma
    • 2
  • Ke-Jun Nan
    • 1
  • Hong-Yi Zhang
    • 1
    • 3
  1. 1.Department of OncologyThe First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anPeople’s Republic of China
  2. 2.Department of OncologyYanan University Affiliated HospitalYan’anPeople’s Republic of China
  3. 3.Department of UrologyYanan University Affiliated HospitalYan’anPeople’s Republic of China
  4. 4.Department of OncologyShaanxi Province Cancer HospitalXi’anPeople’s Republic of China

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