Cited by 3,170Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchCancer Genomics and Diagnostics

Epidermal growth factor receptor mutations in lung cancer

Sharma, Sreenath V., Bell, Daphne W., Settleman, Jeffrey, Haber, Daniel A.·2007·Nature Reviews Cancer

Abstract

The development and clinical application of inhibitors that target the epidermal growth factor receptor (EGFR) provide important insights for new lung cancer therapies, as well as for the broader field of targeted cancer therapies. We review the results of genetic, biochemical and clinical studies focused on somatic mutations of EGFR that are associated with the phenomenon of oncogene addiction, describing 'oncogenic shock' as a mechanistic explanation for the apoptosis that follows the acute treatment of susceptible cells with kinase inhibitors. Understanding the genetic heterogeneity of epithelial tumours and devising strategies to circumvent their rapid acquisition of resistance to targeted kinase inhibitors are essential to the successful use of targeted therapies in common epithelial cancers.

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Crossref · 10.1038/nrc2088

Cites

180 of 180 references verified0 citation errors · 0 not checkable

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  • Overexpression or increased activity of wild-type EGFR protein can lead to cell proliferation, migration, survival, and anti-apoptosis through signaling cascades, which are strongly associated with the occurrence and development of many cancers such as NSCLC, breast cancer, glioma, head and neck cancer, cervical cancer, and bladder cancer.

    “Overexpression or increased activity of wild-type EGFR protein can lead to cell proliferation, migration, survival, and anti-apoptosis through signaling cascades, which are strongly associated with the occurrence and development of many cancers, such as NSCLC, breast cancer, glioma, head and neck cancer, cervical cancer, and bladder cancer.105–108”
  • Activated EGFR induces pro-survival and anti-apoptotic signals through ERK/MAPK and PI3K/AKT.

    “Activated EGFR induces EGFR-mediated pro-survival and anti-apoptotic signals through downstream targets such as extracellular-signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinases (PI3K)/protein kinase B (AKT) [10, 11].”

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Authors
Sharma, S. V., Bell, D. W., Settleman, J., & Haber, D. A.
Affiliations
  • Harvard University (US)
  • National Institutes of Health (US)
Corresponding author
Haber, Daniel A.
Venue
Nature Reviews Cancer
Published
2007-03
Volume
7
Issue
3
Pages
169-181
ISSN
  • 1474-175X (ISSN-L)
  • 1474-1768
OpenAlex
W1967394241
Cited by
3,170
References
182
Citations by year
2026: 85 · 2025: 130 · 2024: 131 · 2023: 168 · 2022: 186 · 2021: 181 · 2020: 175 · 2019: 154 · 2018: 209 · 2017: 213 · 2016: 186 · 2015: 205 · 2014: 191 · 2013: 206 · 2012: 189
FWCI
21.12
Type
journal article
Language
en
Open access
closed
Locations
  • Nature reviews. Cancer (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords
epidermal growth factor receptor, EGFR mutation, lung cancer, tyrosine kinase inhibitors, drug resistance, oncogene addiction, apoptosis, genetic heterogeneity, targeted cancer therapy, epithelial tumors
MeSH terms
Animals, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Mutation, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, ErbB Receptors

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