Small-cell lung cancer articles within Nature Communications

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  • Article
    | Open Access

    Small cell lung cancers (SCLC) have often inactivating mutations in RB1. In this study, the authors demonstrate that RB1 loss mediates low expression of YAP1 in SCLC tumors ultimately promoting metastasis and they propose to use benzamide family HDAC inhibitors to induce YAP1 expression for prevention of metastases.

    • Zhengming Wu
    • , Junhui Su
    •  & Kun-Liang Guan

  • Article
    | Open Access

    p53 inactivation is nearly universal in small-cell lung cancer (SCLC), but its tumor suppressive role in this cancer type is poorly understood. Here the authors show that intertumoral heterogeneity in SCLC influences the biological mechanisms of p53-mediated tumor suppression and identify a role for cyclophilins in p53-dependent necrotic cell death.

    • Jonuelle Acosta
    • , Qinglan Li
    •  & David M. Feldser

  • Article
    | Open Access

    LSD1 inhibition blocks the neuroendocrine phenotype of some small cell lung cancers (SCLCs). Here, a genome-wide CRISPR/Cas9 LSD1 inhibitor resistance screen identifies the mRNA-binding protein ZFP36L1 as a gene repressed by LSD1 that when restored inhibits SCLC neuroendocrine differentiation.

    • Hsiao-Yun Chen
    • , Yavuz T. Durmaz
    •  & Matthew G. Oser

  • Article
    | Open Access

    Molecular subtypes of small cell lung cancer characterized by neuroendocrine differentiation have been described in cell lines and primary tumors. The clinical implications of neuroendocrine subtypes in metastatic and relapsed tumors, and the extent to which the subtype distribution is recapitulated in patient-derived models remains unclear. Here, the authors integrated genomics and transcriptomics on 100 small cell cancers from a range of metastatic sites finding complex intra- and intertumoral heterogeneity, notably not recapitulated in patient-derived model systems, and distinct therapeutic vulnerabilities associated with neuroendocrine subtypes.

    • Delphine Lissa
    • , Nobuyuki Takahashi
    •  & Anish Thomas

  • Article
    | Open Access

    Small-cell lung cancer (SCLC) is an aggressive disease with limited therapeutic options. Here the authors perform an immunogenomic analysis of limited-stage SCLC, revealing a homogeneous mutational landscape, but limited T-cell infiltration and a cold and heterogeneous T cell repertoire.

    • Ming Chen
    • , Runzhe Chen
    •  & Jianjun Zhang

  • Article
    | Open Access

    Multi-region sequencing of small cell lung cancers (SCLC) can improve our understanding of the disease. Here the authors analyse 120 multi-region samples from 40 SCLC patients with whole exome sequencing and characterise their mutational burden, evolution, heterogeneity, and potential prognostic biomarkers.

    • Huaqiang Zhou
    • , Yi Hu
    •  & Ningning Zhou

  • Article
    | Open Access

    DNA from tumour cells can be detected in the blood of cancer patients. Here, the authors show that cell free DNA fragmentation patterns can identify lung cancer patients and when this information is further interrogated it can be used to predict lung cancer histological subtype.

    • Dimitrios Mathios
    • , Jakob Sidenius Johansen
    •  & Victor E. Velculescu

  • Article
    | Open Access

    Immune checkpoint blockade (ICB) benefits only a small subset of patients with small cell lung cancer (SCLC) and the mechanisms driving benefit are poorly understood. Here, the authors show that elevated Notch signaling predicts clinical benefit in ICB in relapsed SCLC.

    • Nitin Roper
    • , Moises J. Velez
    •  & Anish Thomas

  • Article
    | Open Access

    The high degree of subtype plasticity in small cell lung cancer (SCLC) poses a therapeutic challenge. Here, the authors show that the non-neuroendocrine (non-NE) subtype of SCLC is sensitive to ferroptosis while the neuroendocrine (NE) subtype is vulnerable to TRX anti-oxidant pathway inhibition, and the combination of these two treatments in SCLC circumvents non-NE/NE subtype plasticity.

    • Christina M. Bebber
    • , Emily S. Thomas
    •  & Silvia von Karstedt

  • Article
    | Open Access

    The expression of oncogenic MYC paralogs in small cell lung cancer is mutually exclusive. In this study, the authors show that MYC, but not MYCN or MYCL, represses BCL2, resulting in cells that are uniquely sensitive to apoptosis, and find that CHK1 and AURKA inhibitors may be useful for treating these cancers.

    • Marcel A. Dammert
    • , Johannes Brägelmann
    •  & Martin L. Sos

  • Article
    | Open Access

    Cancer cells are metabolically adaptable and the identification of specific vulnerabilities is challenging. Here the authors identify a subset of neuroendocrine cell lines exquisitely sensitive to inhibition of SQLE, an enzyme in the cholesterol biosynthetic pathway, due to the toxic accumulation of pathway intermediate squalene.

    • Christopher E. Mahoney
    • , David Pirman
    •  & Gromoslaw A. Smolen

  • Article
    | Open Access

    Small cell lung cancer (SCLC) patients frequently relapse and become resistant to chemotherapy. Here, the authors analyse the genomic and transcriptomic landscape of primary and relapsed SCLC patients as well as in vitro models, and discover that activation of WNT signalling can drive chemotherapy resistance.

    • Alex H. Wagner
    • , Siddhartha Devarakonda
    •  & Ramaswamy Govindan

  • Article
    | Open Access

    The molecular nature of large-cell neuroendocrine lung carcinomas (LCNEC) has remained unclear. Here, the authors show LCNECs represent a distinct transcriptional subgroup among lung cancers and comprise two molecular subgroups, type I (TP53 and STK11/KEAP1 alterations) and type II (TP53 and RB1 inactivation).

    • Julie George
    • , Vonn Walter
    •  & Roman K. Thomas

  • Article
    | Open Access

    Treatment of small-cell lung cancer remains a challenge due to multiple mechanisms of resistance to current therapies; measuring patient response is crucial in adapting and choosing adequate treatment. Here the authors develop a strategy to visualise in vivo dynamics of a class of widely used PARP inhibitors.

    • Brandon Carney
    • , Susanne Kossatz
    •  & Thomas Reiner

  • Article
    | Open Access

    Small cell lung cancer (SCLC) is characterised by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. The authors show that SCLC patients have a rare CTC subset with a vasculogenic mimicry (VM) phenotype, and that VM is associated with worse overall survival, and alters tumour growth, chemotherapy delivery and efficacy.

    • Stuart C. Williamson
    • , Robert L. Metcalf
    •  & Caroline Dive

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