EphB4: A promising target for upper aerodigestive malignancies

Our plain-English summary of EphB4: A promising target for upper aerodigestive malignancies, by R. Salgia, P. Kulkarni, P.S. Gill (Biochimica et Biophysica Acta. Reviews on Cancer, 2018).

The study

• Authors: R. Salgia, P. Kulkarni, P.S. Gill
• Journal: Biochimica et Biophysica Acta. Reviews on Cancer
• Published: 2018;1869(2):128-137
• Type of article: Review
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The erythropoietin-producing hepatocellular carcinoma (Eph) receptors are the largest family of receptor tyrosine kinases (RTKs) that include two major subclasses, EphA and EphB. They form an important cell communication system with critical and diverse roles in a variety of biological processes during embryonic development. However, dysregulation of the Eph/ephrin interactions is implicated in cancer contributing to tumour growth, metastasis, and angiogenesis. Here, we focus on EphB4 and review recent developments in elucidating its role in upper aerodigestive malignancies to include lung cancer, head and neck cancer, and mesothelioma. In particular, we summarize information regarding EphB4 structure/function and role in disease pathobiology. We also review the data supporting EphB4 as a potential pharmacological and immunotherapy target and finally, progress in the development of new therapeutic strategies including small molecule inhibitors of its activity is discussed. The emerging picture suggests that EphB4 is a valuable and attractive therapeutic target for upper aerodigestive malignancies.

Copyright © 2018 Elsevier B.V. All rights reserved.

In plain English

This article was a review, not a new study. The authors summarized published research on EphB4, a receptor protein found on cell surfaces, in lung cancer, head and neck squamous cell carcinoma, and malignant mesothelioma. They also discussed experimental drugs and immune treatments aimed at EphB4. Asbestos came up only as background: the authors noted that malignant pleural mesothelioma often develops decades after asbestos exposure. No asbestos exposure was studied. Among the mesothelioma studies reviewed, Xia et al (2005) reported that EphB4 was highly expressed in mesothelioma cell lines and tumour tissue but not in normal mesothelium. Liu et al (2013) reported EphB4 overexpressed in 72% of surgical mesothelioma specimens, with 85% given for the epithelioid and 38% for the sarcomatoid subtype. In Liu et al's mouse experiments, a soluble EphB4 inhibitor inhibited tumour growth, and combining it with bevacizumab led to complete tumour regression. The authors noted that no non-synonymous EphB4 mutations had been reported in pleural mesothelioma tissue. They concluded that the reviewed data point to a cancer-promoting role for EphB4 in these cancers. They added that its use as a prognostic marker needs more study.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: narrative review of published laboratory, animal and patient studies
• Who was studied: Published studies on EphB4 in lung cancer, head and neck cancer and mesothelioma, including cell lines, mouse xenograft models and patient tissue samples; no search method or number of included studies is given
• Exposure: No asbestos exposure was studied. The review concerns the EphB4 receptor and treatments targeting it. Asbestos is mentioned only as background to malignant pleural mesothelioma.
• Main results:
  • Reviewed study (Xia et al, 2005): EphB4 was highly expressed in mesothelioma cell lines and primary tumour tissues but not in normal mesothelium. Knocking it down reduced cell survival, migration and invasion.
  • Reviewed study (Liu et al, 2013): in surgical samples of human mesothelioma tissue, EphB4 was overexpressed in 72% of specimens, with 85% given for epithelioid and 38% for sarcomatoid subtypes
  • Reviewed study (Liu et al, 2013), mice with mesothelioma xenograft tumours: the inhibitor sEphB4-HSA inhibited tumour growth on its own. Combined with bevacizumab, it led to complete tumour regression.
  • No non-synonymous EphB4 mutations had been reported in head and neck squamous cell carcinoma or pleural mesothelioma tissues
  • Reviewed study (Ferguson et al, 2015), lung cancer samples: non-synonymous EphB4 mutations occurred in 7% of samples (9% in adenocarcinoma, 9% in small cell lung cancer, 3% in squamous cell carcinoma)
  • Reviewed study (Sinha et al, 2006), 48 patients with head and neck squamous cell carcinoma: EphB4 expression was statistically significantly higher in advanced-stage disease than in early-stage disease, and in smokers than in nonsmokers
• The authors' conclusion: The authors concluded that the data they reviewed point to a cancer-promoting (oncogenic) rather than tumour-suppressing role for EphB4 in lung cancer, head and neck squamous cell carcinoma and malignant mesothelioma
• Limitations the authors state:
  • EphB4's possible use as a prognostic biomarker rests on preliminary studies with small patient groups and needs further study
  • Because Eph receptor interactions have been shown both to promote and to inhibit tumour growth, their role in cancer remains debated
  • No CAR T-cell therapy studies targeting EphB4 had been reported

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Carcinoma, Metastasis, Angiogenesis, Lung Cancer, Mesothelioma, Immunotherapy.

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• Influence of inter-observer delineation variability on radiomics stability in different tumor sites — M. Pavic, M. Bogowicz, et al. (2018)
• Occupational dust exposure and head and neck squamous cell carcinoma risk in a population-based case-control study conducted in the greater Boston area — S.M. Langevin, M.D. McClean, et al. (2013)
• Occupational exposures and squamous cell carcinoma of the oral cavity, pharynx, larynx, and oesophagus: a case-control study in Sweden — P. Gustavsson, R. Jakobsson, et al. (1998)

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