The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly dividing de‐differentiated state
Open accessAbstract
Treatment of BRAF ‐mutant melanomas with MAP kinase pathway inhibitors is paradigmatic of the promise of precision cancer therapy but also highlights problems with drug resistance that limit patient benefit. We use live‐cell imaging, single‐cell analysis, and molecular profiling to show that exposure of tumor cells to RAF / MEK inhibitors elicits a heterogeneous response in which some cells die, some arrest, and the remainder adapt to drug. Drug‐adapted cells up‐regulate markers of the neural crest (e.g., NGFR ), a melanocyte precursor, and grow slowly. This phenotype is transiently stable, reverting to the drug‐naïve state within 9 days of drug withdrawal. Transcriptional profiling of cell lines and human tumors implicates a c‐Jun/ ECM / FAK /Src cascade in de‐differentiation in about one‐third of cell lines studied; drug‐induced changes in c‐Jun and NGFR levels are also observed in xenograft and human tumors. Drugs targeting the c‐Jun/ ECM / FAK /Src cascade as well as BET bromodomain inhibitors increase the maximum effect ( E max ) of RAF / MEK kinase inhibitors by promoting cell killing. Thus, analysis of reversible drug resistance at a single‐cell level identifies signaling pathways and inhibitory drugs missed by assays that focus on cell populations.
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Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
Trapnell, C., Williams, B. A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M. J., Salzberg, S. L., Wold, B. J., & Pachter, L. (2010) · Nature Biotechnology · doi:10.1038/nbt.1621 · Cited by 15,556
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
Barretina, J., Caponigro, G., Stransky, N., Venkatesan, K., Margolin, A. A., Kim, S., Wilson, C. J., Lehár, J., Kryukov, G. V., Sonkin, D., et al. (2012) · Nature · doi:10.1038/nature11003 · Cited by 7,950
Self-citationDissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Tirosh, I., Izar, B., Prakadan, S. M., Wadsworth, M. H., Treacy, D., Trombetta, J. J., Rotem, A., Rodman, C., Lian, C., Murphy, G., et al. (2016) · Science · doi:10.1126/science.aad0501 · Cited by 4,944
Self-citationGenomic classification of cutaneous melanoma
Akbani, R., Akdemir, K. C., Aksoy, B. A., Albert, M., Ally, A., Amin, S. B., Arachchi, H., Arora, A., Auman, J. T., Ayala, B., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.044 · Cited by 3,151
Self-citationRAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)
Poulikakos, P. I., Persaud, Y., Janakiraman, M., Kong, X., Ng, C., Moriceau, G., Shi, H., Atefi, M., Titz, B., Gabay, M. T., et al. (2011) · Nature · doi:10.1038/nature10662 · Cited by 1,454
Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma
Sun, C., Wang, L., Huang, S., Heynen, G. J. J. E., Prahallad, A., Robert, C., Haanen, J., Blank, C., Wesseling, J., Willems, S. M., et al. (2014) · Nature · doi:10.1038/nature13121 · Cited by 888
Cited by
Tsoi, J., Robert, L., Paraiso, K., Galvan, C., Sheu, K. M., Lay, J., Wong, D. J. L., Atefi, M., Shirazi, R., Wang, X., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.017 · Cited by 938
Toward Minimal Residual Disease-Directed Therapy in Melanoma
Rambow, F., Rogiers, A., Marin-Bejar, O., Aibar, S., Femel, J., Dewaele, M., Karras, P., Brown, D., Chang, Y. H., Debiec-Rychter, M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.025 · Cited by 771
Lineage plasticity in cancer: a shared pathway of therapeutic resistance
Quintanal-Villalonga, Á., Chan, J. M., Yu, H. A., Pe’er, D., Sawyers, C. L., Sen, T., & Rudin, C. M. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0340-z · Cited by 572
Combining epigenetic drugs with other therapies for solid tumours — past lessons and future promise
Morel, D., Jeffery, D., Aspeslagh, S., Almouzni, G., & Postel-Vinay, S. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0267-4 · Cited by 445
Keenan, A. B., Jenkins, S. L., Jagodnik, K. M., Koplev, S., He, E., Torre, D., Wang, Z., Dohlman, A. B., Silverstein, M. C., Lachmann, A., et al. (2018) · Cell Systems · doi:10.1016/j.cels.2017.11.001 · Cited by 423
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Metadata
- Authors
- Fallahi‐Sichani, M., Becker, V., Izar, B., Baker, G. J., Lin, J., Boswell, S. A., Shah, P., Rotem, A., Garraway, L. A., & Sorger, P. K.
- Venue
- Molecular Systems Biology
- Published
- 2017-01
- Volume
- 13
- Issue
- 1
- Pages
- 905-905
- ISSN
- 1744-4292 (ISSN-L)
- OpenAlex
- W2569342357
- Cited by
- 235
- References
- 18
- FWCI
- 9.71
- Type
- journal article
- Language
- en
- Open access
- gold
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- Fallahi‐Sichani, M., Becker, V., Izar, B., Baker, G. J., Lin, J., Boswell, S. A., Shah, P., Rotem, A., Garraway, L. A., & Sorger, P. K. (2017). Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly dividing de‐differentiated state. Molecular Systems Biology. https://doi.org/10.15252/msb.20166796
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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.
