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. 2021 Dec 27;40(4):1141–1157. doi: 10.1007/s10555-021-10012-4

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — Therapeutic targets and treatment opportunities during the transdifferentiation of SCLC. A recent study has described that there is a temporal shift from SCLC-A to SCLC-N then to SCLC-Y subtypes instead of a permanent subtype [97]. This transdifferentiation process inversely correlates with the prevalence of the cases as well as the NE-marker expression. Each step (or subtype) is characterized by distinct vulnerabilities that can be therapeutically exploited. Acquired resistance to platinum-based chemotherapy (marked with gray color) develops in almost all cases; however, mTOR and metabolic alterations may provide additional therapeutic targets in resistant SCLC cases (marked with blue color)