Small Cell Lung Cancer (SCLC)

Overview

Small cell lung cancer (SCLC) is a neuroendocrine carcinoma of the lung characterized by neuroendocrine differentiation, near-universal loss of TP53 and RB1, and extremely aggressive clinical behavior. On OncoTree it is a child of Lung Neuroendocrine Tumor (LNET). SCLC accounts for ~13–15% of lung cancers and is almost exclusively found in smokers. It is typically sensitive to initial chemotherapy but rapidly acquires resistance.

Cohorts in the corpus

  • Included as one of 22 cancer site-of-origin classes in the ATLAS classifier; ATLAS differentiation score distinguished NSCLC from SCLC with AUC=0.963, enabling RNA-based identification of neuroendocrine transformation (zero-shot learning property). PMID:27634761

Recurrent alterations

  • This corpus study does not provide gene-level SCLC mutation frequencies from primary clinical cohorts. The ATLAS classifier uses ~632 RNA expression features for classification rather than genomic alteration profiles.
  • BET bromodomain inhibition showed synthetic lethality in ARID1A-mutant cancers including SCLC cell lines PMID:22037554
  • CLCGP WES/WGS of 29 SCLC tumors revealed universal biallelic inactivation of TP53 and RB1, with frequent amplification of SOX2 and MYCL PMID:22941188
  • JHU WES/WGS of 36 SCLC tumors confirmed biallelic TP53+RB1 loss and highlighted SOX2 amplification and MYCL amplification as recurrent oncogenic events PMID:22941189
  • Comprehensive genomic analysis of SCLC revealed near-universal RB1 and TP53 loss, recurrent CREBBP/EP300 alterations, and NOTCH pathway mutations defining therapeutic vulnerabilities PMID:26168399
  • EZH2-mediated H3K27me3 spreading silences SLFN11 in 4/10 chemoresistant PDX models; EZH2 inhibitor EPZ011989 (tazemetostat homolog) re-expresses SLFN11 and restores cisplatin/etoposide sensitivity in vivo PMID:28196596
  • In the MSK-IMPACT pan-cancer cohort, SCLC had one of the highest TP53 mutation rates at 85% of samples — ranking alongside HGSOC (98%) and esophageal adenocarcinoma (89%). PMID:28481359

Subtypes

  • ATLAS classifier demonstrated AUC=0.963 for distinguishing NSCLC from SCLC by lineage de-differentiation score, supporting RNA-based neuroendocrine identification in clinical contexts. PMID:27634761

Therapeutic landscape

  • The ATLAS lineage de-differentiation score identifies neuroendocrine transformation and anaplastic phenotypes, which are associated with worse prognosis and may guide treatment escalation or de-escalation decisions. PMID:27634761

Sources

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