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NRG1-ErbB Lost in Translation: A New Paradigm for Lung Cancer?

Domenico Trombetta1, Antonio Rossi2, Federico P Fabrizio1

  • 1Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo (FG), Italy.

Current Medicinal Chemistry
|September 14, 2017
PubMed
Abstract

Insights

New NRG1 gene lesions in lung cancer activate ErbB2/ErbB3 signaling. Understanding this ErbB/PI3K-AKT axis deregulation aids patient stratification and targeted therapies, like NRG1-ErbB3 inhibitors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Molecular lesions of the NRG1 gene are a new feature in Invasive Mucinous Adenocarcinoma of the lung.
  • NRG1 fusions activate ErbB2/ErbB3 signaling through PI3K-AKT and MAPK pathways.
  • ErbB receptor deregulation is implicated in various solid tumors.

Purpose of the Study:

  • To review current knowledge of the ErbB network and NRG1 deregulation in lung cancer.
  • To explore the ErbB/PI3K-AKT axis and its modulation by pharmacologic strategies.
  • To highlight novel molecular markers for patient stratification.

Main Methods:

  • Structured literature search of bibliographic databases.
  • Assessment of retrieved papers using standard tools; 135 papers included.
  • Screening of papers on ErbB receptor lesions, NRG1 function, and NRG1 fusions in lung cancer.

Main Results:

  • NRG1 gene lesions lead to aberrant activation of ErbB2/ErbB3 signaling.
  • ErbB pathway deregulation provides insights into lung cancer molecular status.
  • Novel molecular markers for patient stratification were identified.

Conclusions:

  • Understanding ErbB pathway deregulation aids in identifying new molecular markers for lung cancer patient stratification.
  • Inhibitors targeting the NRG1-ErbB3 interaction offer a strategy to block ErbB intracellular signaling.
  • Pharmacologic strategies targeting the ErbB/PI3K-AKT axis are emerging for lung cancer treatment.
Keywords:
ErbB networkErbB3NRG1 fusionlung cancerresistance to therapytarget therapy

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