The subtyping of LCNEC has opened possibilities for stratification in therapy: LCNEC, which have lost RB1 have been shown to respond to SCLC-like chemotherapy, whereas those retaining RB1 (Figure 2) and having either loss of PTEN, activating mutation of PI3KCA, combined with mutations of TP53, respectively, respond better to cisplatin chemotherapy (33, 36). Here, PTEN is linked to large cell neuroendocrine carcinoma.