As already mentioned, alterations in PI3K/AKT/mTOR pathway have been found in LCNEC, in particular PIK3CA mutations, PTEN loss, PIK3CA CNV, and RICTOR CNV (42, 44), but no compounds have been developed to target these potential driver alterations in LCNEC patients. This evidence concerns the gene PTEN and large cell neuroendocrine carcinoma.