The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Single-cell analyses reveal increased intratumoral heterogeneity after the onset of therapy resistance in small-cell lung cancer
Open accessAbstract
The natural history of small-cell lung cancer (SCLC) includes rapid evolution from chemosensitivity to chemoresistance, although mechanisms underlying this evolution remain obscure due to the scarcity of post-relapse tissue samples. We generated circulating tumor cell (CTC)-derived xenografts from patients with SCLC to study intratumoral heterogeneity (ITH) via single-cell RNA sequencing of chemosensitive and chemoresistant CTC-derived xenografts and patient CTCs. We found globally increased ITH, including heterogeneous expression of therapeutic targets and potential resistance pathways, such as epithelial-to-mesenchymal transition, between cellular subpopulations following treatment resistance. Similarly, serial profiling of patient CTCs directly from blood confirmed increased ITH post-relapse. These findings suggest that treatment resistance in SCLC is characterized by coexisting subpopulations of cells with heterogeneous gene expression leading to multiple, concurrent resistance mechanisms. These findings emphasize the need for clinical efforts to focus on rational combination therapies for treatment-naïve SCLC tumors to maximize initial responses and counteract the emergence of ITH and diverse resistance mechanisms. Stewart et al. use circulating tumor cell-derived xenografts from patients with small-cell lung cancer to study tumor heterogeneity following the onset of therapeutic resistance.
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Integrating single-cell transcriptomic data across different conditions, technologies, and species
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Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
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Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing
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Self-citationSkoulidis, F., Byers, L. A., Diao, L., Papadimitrakopoulou, V. A., Tong, P., Izzo, J., Behrens, C., Kadara, H., Parra, E. R., Canales, J. R., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-1236 · Cited by 936
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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., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2020.12.014 · Cited by 962
Self-citationIreland, A. S., Micinski, A. M., Kastner, D. W., Guo, B., Wait, S. J., Spainhower, K. B., Conley, C. C., Chen, O. S., Guthrie, M. R., Soltero, D., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.05.001 · Cited by 508
Self-citationChan, J. M., Quintanal-Villalonga, Á., Gao, V. R., Xie, Y., Allaj, V., Chaudhary, O., Masilionis, I., Egger, J., Chow, A., Walle, T., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.09.008 · Cited by 434
Self-citationMegyesfalvi, Z., Gay, C. M., Popper, H., Pirker, R., Ostoros, G., Heeke, S., Lang, C., Hoetzenecker, K., Schwendenwein, A., Boettiger, K., et al. (2023) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21785 · Cited by 369
Self-citationIntrinsic Immunogenicity of Small Cell Lung Carcinoma Revealed by Its Cellular Plasticity
Mahadevan, N. R., Knelson, E. H., Wolff, J. O., Vajdi, A., Saigí, M., Campisi, M., Hong, D., Thai, T. C., Piel, B., Han, S., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0913 · Cited by 227
Metadata
- Authors
- Stewart, C. A., Gay, C. M., Xi, Y., Sivajothi, S., Sivakamasundari, V., Fujimoto, J., Bolisetty, M., Hartsfield, P. M., Balasubramaniyan, V., Chalishazar, M. D., Moran, C., Kalhor, N., Stewart, J., Tran, H., Swisher, S. G., Roth, J. A., Zhang, J., de Groot, J., Glisson, B., Oliver, T. G., Heymach, J. V., Wistuba, I., Robson, P., Wang, J., & Byers, L. A.
- Venue
- Nature Cancer
- Published
- 2020-02-17
- Volume
- 1
- Issue
- 4
- Pages
- 423-436
- ISSN
- 2662-1347 (ISSN-L)
- OpenAlex
- W3006044557
- Cited by
- 366
- References
- 7
- FWCI
- 16.28
- Type
- journal article
- Language
- en
- Open access
- green
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- Stewart, C. A., Gay, C. M., Xi, Y., Sivajothi, S., Sivakamasundari, V., Fujimoto, J., Bolisetty, M., Hartsfield, P. M., Balasubramaniyan, V., Chalishazar, M. D., Moran, C., Kalhor, N., Stewart, J., Tran, H., Swisher, S. G., Roth, J. A., Zhang, J., de Groot, J., Glisson, B., . . . Byers, L. A. (2020). Single-cell analyses reveal increased intratumoral heterogeneity after the onset of therapy resistance in small-cell lung cancer. Nature Cancer. https://doi.org/10.1038/s43018-019-0020-z
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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