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An alternative driver of SCLC metastasis illustrates the cancer’s plasticity

Julien Sage, Ludwig Cancer Research Stanford
Julien Sage

Previous studies conducted with mouse models and on patient tumors have implicated the transcription factor NFIB as a primary driver of the growth and metastasis of small cell lung cancer (SCLC), an aggressive cancer that metastasizes readily. A study led by Ludwig Stanford’s Julien Sage used conditional gene knockout strategies in genetically engineered mouse models of the cancer to establish NFIB’s role in tumor progression and metastasis and its suitability as a drug target for SCLC treatment. They reported in a November paper in Cancer Research that while heightened activity of NFIB contributes to tumor progression, the protein is not absolutely required for metastasis. Instead, the researchers identify transcription factors FOXA1 and FOXA2—pioneer transcription factors that can, unlike most transcription factors, interact with inactive regions of chromosomes and activate silent genes—as candidate drivers of SCLC metastasis. Julien and his colleagues point out that this alternative pathway to metastasis in SCLC highlights the notable plasticity of this cancer. Beyond that, the finding identifies additional targets for the treatment of the generally lethal cancer.

Small cell lung cancer plasticity enables NFIB-independent metastasis
Cancer Research, 2023 November 14

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