NRG1-ErbB lost in translation: a new paradigm for lung cancer?

5 years ago

NRG1-ErbB lost in translation: a new paradigm for lung cancer?

Fazio VM, Sparaneo A, Trombetta D, Fabrizio FP, Muscarella LA, Graziano P, Rossi A

The ErbB network of receptor tyrosine kinases represents one of the best examples of how the understanding of molecular basis of tumor pathogenesis can give a significant improvement for patients treatment, suggesting new therapeutic options to overcome acquired treatment resistance. This amazing bridge between growth factor receptors and cancer has been consolidated during the last decades through the identification of many driver mutations in the gene key of the RTKs network. Unexpected molecular lesions of the NRG1 gene followed by an aberrant ErbB signaling were recently described as a new molecular features of non-small cell lung cancer, but it has been also sporadically reported in other tumors. The NRG1 chimeric ligand leads to aberrant activation of the ErbB2-ErbB3 heterodimers signaling pathways via PI3K-AKT and MAPK cascades in cancers of the breast, lung, brain, head and neck, and colon. Molecular lesions of the ErbB network and PI3K-AKT are well-investigated in lung cancer and actually represent one of the main interesting targets for the current pharmacological studies. However, new insights into this picture are strongly needed to increase its translational impact. We highlight the current knowledge about the ErbB network and NRG1 deregulation in lung cancer and their merger into the ErbB/PI3K-AKT axis modulation and current therapeutic strategies. Several drugs targeting ErbB2, ErbB3 and their downstream pathways in different stages of clinical development are actually available. More advances in knowledge of crosstalk between NRG1, ErbB3 and PI3K-AKT pathways may increase and strongly support the therapeutic choice for lung cancer patients.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28901268

DOI: PubMed:28901268