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. 2024 Jan 19;10(3):eadh2579. doi: 10.1126/sciadv.adh2579

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Copyright © 2024 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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Fig. 1. — (A) Structure of talazoparib. (B) Value of IC₅₀ in a total of 24 SCLC cell lines treated with talazoparib. SCLC cell lines are indicated as ASCL1^high, NEUROD1^high, POU2F3^high, or TF^low subtype. The sensitivity is defined as: sensitive (red), IC₅₀ < 1 μM; resistant (blue), IC₅₀ > 1 μM. TF^low, low expression of all three TFs. (C) Workflow of high-throughput multiplexed quantitative proteome mapping in a total of 96 proteome samples including a total of 24 SCLC lines treated with or without talazoparib (1 μM for 48 hours) in a total of six Tandem Mass Tag (TMT) experiments. (D) Steps of the identification of PARPi-induced protein degradation signature (PiPS) proteins only identified in PARPi-sensitive ASCL1^high SCLC subtype. Volcano plots show differentially expressed proteins in talazoparib treatment in each PARPi-sensitive and PARPi-resistant ASCL1^high SCLC subtype [log₂ fold change (log₂FC) < −0.3, P < 0.05]. Venn diagram shows the number of identified PiPS proteins. (E) Gene Ontology (GO) analyses of PiPS proteins identified in PARPi-sensitive ASCL1^high SCLC subtype. Biological processes were analyzed using the ToppGene database (https://toppgene.cchmc.org/). LC-MS/MS, liquid chromatography tandem MS; m/z, mass-charge ratio.