Project description:Small Cell Lung Cancer (SCLC) is an aggressive neuroendocrine malignancy with a poor prognosis. Here, we focus on the neuroendocrine SCLC subtypes SCLC-A and SCLC-N, whose transcription addiction was driven by ASCL1 and NEUROD1 transcription factors which target E-box motifs to activate up to 40% of total genes, the promoters of which are maintained in a steadily open chromatin environment according to ATAC and H3K27Ac signatures. This leverage is used by the marine agent lurbinectedin, which preferentially targets the CpG islands located downstream of the transcription start site, thus arresting elongating RNAPII and promoting its degradation. This abrogates the expression of ASCL1 and NEUROD1 and of their dependent genes such as BCL2, INSM1, MYC and AURKA, which are responsible for relevant SCLC tumorigenic properties such as inhibition of apoptosis and cell survival, as well as for a part of its neuroendocrine features. In summary, we show how the transcription addiction of these cells becomes their Achilles' heel, and how this is effectively exploited by lurbinectedin as a novel and highly specific SCLC therapeutic endeavor.

2022-02-03 | GSE195663 | GEO

PM01183 on SCLC cell lines Chem-seq

Project description:Chem seq to compare the binding activity of biotynilated drugs.Lurbinectedin and cisplatin comparison

2022-01-29 | GSE190398 | GEO

RNAseq analysis of small cell lung cancer (SCLC) cell lines

Project description:Small cell lungcancer (SCLC) is an aggressive malignancy with dismal clinical outcomes, due inpart to the scarcity of post-relapse tissue samples. To understand more of transcriptional changes associated with treatment resistance, we performed RNAseq analysis of 61 SCLC cell lines.

2020-11-24 | GSE151904 | GEO

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