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. 2022 Aug 3;14(15):3772. doi: 10.3390/cancers14153772

Figure 3.

Figure 3

(A–C). Representation of plasticity and intratumoral heterogeneity leading to chemoresistance and metastasis in SCLC subtypes. (A) MYC drives the temporal evolution of SCLC-A to SCLC-N to SCLC expressing YAP1 [54]. The former two are NE subtypes and the latter, a low NE subtype. SCLCs expressing YAP1 have been shown to demonstrate multidrug resistance [60]; (B) Acquired resistance to platinum-based chemotherapies leads to a decrease in the proportion of SCLC-A cells, and an increase in the SCLC-I proportion [10]. SCLC-I cells are platinum-resistant and have higher EMT scores, suggesting that subtype switching could underlie platinum resistance. SCLCs with acquired resistance to platinum-based chemotherapies are molecularly heterogeneous compared to their treatment-naïve counterparts [55]; (C) SCLC-P is a distinct subtype of SCLC rarely co-expressing other subtypes or YAP1. An association between SCLC-P and combined SCLC (with lung adenocarcinoma) has been made [43,58]. SCLC-P is a low NE subtype that is retained in primary and metastatic tumors [58]. (LUAD; lung adenocarcinoma).