Non-neuroendocrine differentiation generates a ferroptosis-prone lipidome in small cell lung cancer (SCLC)

Christina M Bebber; Silvia von Karstedt

doi:10.1080/23723556.2021.1933871

Non-neuroendocrine differentiation generates a ferroptosis-prone lipidome in small cell lung cancer (SCLC)

Mol Cell Oncol. 2021 Jul 5;8(4):1933871. doi: 10.1080/23723556.2021.1933871. eCollection 2021.

Authors

Christina M Bebber^{1

2}, Silvia von Karstedt^{1

2

3}

Affiliations

¹ Department of Translational Genomics, Medical Faculty, University of Cologne, Cologne, Germany.
² CECAD Cluster of Excellence, University of Cologne, Cologne, Germany.
³ Center for Molecular Medicine Cologne, Medical Faculty, University Hospital of Cologne, Cologne, Germany.

Abstract

Our recent study revealed that non-neuroendocrine small cell lung cancer (SCLC) is sensitive to the induction of ferroptosis due to upregulation of ether lipid synthesis. While neuroendocrine SCLC is ferroptosis resistant, it acquires addiction to the thioredoxin pathway. Combined redox pathway targeting therefore achieves efficient anti-tumor activity in heterogenous SCLC.

Keywords: Ferroptosis; GPX4; GSH; PUFA; SCLC; cell death; ether lipids; lipid peroxidation; neuroendocrine cancer; thioredoxin.

Grants and funding

This work was supportedby the German Cancer Aid (Deutsche Krebshilfe) [Max-Eder-Project 701125509], a project grant [432038712], a collaborative research center grant on SCLC [SFB1399, A05], a collaborative research center grant on cell death [SFB1403, A05] all funded by the German Research Foundation [Deutsche Forschungsgemeinschaft, DFG], by an eMed consortium grant [01ZX1901] funded by the German state (BMBF) and a project grant [A06] funded by the center for molecular medicine (CMMC), Cologne, Germany.