NRG/ErbB signaling: on the trail of a molecular fingerprint in mucinous carcinoma

Human neuregulins (NRG) are small epidermal growth factor ligands involved in the activation of ErbBs receptors. Among genomic aberrations, NRG fusions are one of the most intriguing genetic markers reported in the latest years, due to their agnostic and potentially predictive features. Mucinous carcinoma showed a higher rate of mutations in downstream effectors of NRG/ErbB activation, thus suggesting that RAS/MAPK and PIK3K/AKT pathway are involved in mucinous phenotype development and aggressiveness.

Epidemiological data on the spectrum of all NRG/ErbBs and downstream effectors alterations in mucinous carcinoma of digestive tract, ovary, lung, and pancreato-biliary tract, as well as their correlation with respective immunological and molecular background are discussed. Peer-reviewed publications on high-quality international from PubMed and data from scientific official sites were used to update the current literature.

Recent scientific advances highlight the predictive and prognostic role of the NRGs/ErbBs network deregulation in cancer; anyhow its role is not well investigated in solid tumors with mucinous features. Although the mucin-rich cancers have a considerably greater rate of mutations in therapeutically critical pathways than non-mucinous ones, common mucinous pathways have not yet been found.