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Cited by 962

The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.

Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities

Open access
Gay, Carl M., Stewart, C. Allison, Park, Elizabeth M., Diao, Lixia, Groves, Sarah M., Heeke, Simon, Nabet, Barzin Y., Fujimoto, Junya, Solis, Luisa M., Lu, Wei, Xi, Yuanxin, Cardnell, Robert J., Wang, Qi, Fabbri, Giulia, Cargill, Kasey R., Vokes, Natalie I., Ramkumar, Kavya, Zhang, Bingnan, Della Corte, Carminia M., Robson, Paul, Swisher, Stephen G., Roth, Jack A., Glisson, Bonnie S., Shames, David S., Wistuba, Ignacio I., Wang, Jing, Quaranta, Vito, Minna, John, Heymach, John V., Byers, Lauren Averett·2021·Cancer Cell
DOI 10.1016/j.ccell.2020.12.014
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Abstract

Despite molecular and clinical heterogeneity, small cell lung cancer (SCLC) is treated as a single entity with predictably poor results. Using tumor expression data and non-negative matrix factorization, we identify four SCLC subtypes defined largely by differential expression of transcription factors ASCL1, NEUROD1, and POU2F3 or low expression of all three transcription factor signatures accompanied by an Inflamed gene signature (SCLC-A, N, P and I, respectively). SCLC-I experiences the greatest benefit from the addition of immunotherapy to chemotherapy, while the other subtypes each have distinct vulnerabilities, including to inhibitors of PARP, Aurora kinases, or BCL-2. Cisplatin treatment of SCLC-A patient-derived xenografts induces intratumoral shifts toward SCLC-I, supporting subtype switching as a mechanism of acquired platinum resistance. We propose that matching baseline tumor subtype to therapy, as well as manipulating subtype switching on therapy, may enhance depth and duration of response for SCLC patients.

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Metadata

Authors
Gay, C. M., Stewart, C. A., Park, E. M., Diao, L., Groves, S. M., Heeke, S., Nabet, B. Y., Fujimoto, J., Solis, L. M., Lu, W., Xi, Y., Cardnell, R. J., Wang, Q., Fabbri, G., Cargill, K. R., Vokes, N. I., Ramkumar, K., Zhang, B., Della Corte, C. M., Robson, P., Swisher, S. G., Roth, J. A., Glisson, B. S., Shames, D. S., Wistuba, I. I., Wang, J., Quaranta, V., Minna, J., Heymach, J. V., & Byers, L. A.
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2021-03
Volume
39
Issue
3
Pages
346-360.e7
ISSN
1535-6108 (ISSN-L)
DOI
10.1016/j.ccell.2020.12.014
OpenAlex
W3124749091
Cited by
962
References
62
FWCI
49.41
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities. https://app.cochat.ai/papers/10.1016/j.ccell.2020.12.014
The paper
Gay, C. M., Stewart, C. A., Park, E. M., Diao, L., Groves, S. M., Heeke, S., Nabet, B. Y., Fujimoto, J., Solis, L. M., Lu, W., Xi, Y., Cardnell, R. J., Wang, Q., Fabbri, G., Cargill, K. R., Vokes, N. I., Ramkumar, K., Zhang, B., Della Corte, C. M., . . . Byers, L. A. (2021). Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities. Cancer Cell. https://doi.org/10.1016/j.ccell.2020.12.014

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.