Background: Molecular lesions of the NRG1 gene were recently described as a
new molecular feature of Invasive Mucinous Adenocarcinoma of the lung. The NRG1 chimeric
ligand leads to aberrant activation of the ErbB2/ErbB3 signaling via PI3K–AKT and
MAPK cellular cascades. This review aims to highlight the current knowledge about the ErbB
network and the effect of NRG1 deregulation in lung cancer and their merger into the
ErbB/PI3K-AKT axis modulation by current pharmacologic strategies.
Methods: We performed a structured search of bibliographic databases for peer-reviewed literature
to outline the state of the art with regard ErbB signaling deregulation and NRG1 function
in lung cancer. The quality of retrieved papers was assessed using standard tools and one
hundred thirty-five were included in the review. In many papers the molecular lesions affecting
the ErbB receptors in lung cancer but also in other type of solid tumors were updated. Papers
describing the physiological role of NRG1 in cells was also screened for the review
preparation, as well as the paper reporting NRG1 fusions in lung cancer and their implication
in aberrant ErbB pathway activation.
Results and Conclusion: Overall, this review highpoints how the knowledge of new molecular
mechanisms of ErbB pathway deregulation may help in gaining new insights into the molecular
status of lung cancer patients and unveil a novel molecular markers of patients' stratification.
Moreover, this ultimately led the selection of new compounds designed to inhibit the
bound between Nrg1-ErbB3 as a good alternative way to block the ErbB intracellular signaling.