The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Chromosomal instability determines taxane response
Open accessAbstract
Microtubule-stabilizing (MTS) agents, such as taxanes, are important chemotherapeutics with a poorly understood mechanism of action. We identified a set of genes repressed in multiple cell lines in response to MTS agents and observed that these genes are overexpressed in tumors exhibiting chromosomal instability (CIN). Silencing 22/50 of these genes, many of which are involved in DNA repair, caused cancer cell death, suggesting that these genes are involved in the survival of aneuploid cells. Overexpression of these “CIN-survival” genes is associated with poor outcome in estrogen receptor–positive breast cancer and occurs frequently in basal-like and Her2-positive cases. In diploid cells, but not in chromosomally unstable cells, paclitaxel causes repression of CIN-survival genes, followed by cell death. In the OV01 ovarian cancer clinical trial, a high level of CIN was associated with taxane resistance but carboplatin sensitivity, indicating that CIN may determine MTS response in vivo. Thus, pretherapeutic assessment of CIN may optimize treatment stratification and clinical trial design using these agents.
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Gascoigne, K. E., & Taylor, S. S. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.07.002 · Cited by 832
Duesberg, P., Stindl, R., & Hehlmann, R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.201398998 · Cited by 106
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Matthews, H. K., Bertoli, C., & de Bruin, R. A. M. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00404-3 · Cited by 1,506
Tumour heterogeneity and the evolution of polyclonal drug resistance
Burrell, R. A., & Swanton, C. (2014) · Molecular Oncology · doi:10.1016/j.molonc.2014.06.005 · Cited by 417
Self-citationMitotic chromosomal instability and cancer: mouse modelling of the human disease
Schvartzman, J.-M., Sotillo, R., & Benezra, R. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2781 · Cited by 414
Holland, A. J., & Cleveland, D. W. (2012) · EMBO reports · doi:10.1038/embor.2012.55 · Cited by 288
Metadata
- Authors
- Swanton, C., Nicke, B., Schuett, M., Eklund, A. C., Ng, C., Li, Q., Hardcastle, T., Lee, A., Roy, R., East, P., Kschischo, M., Endesfelder, D., Wylie, P., Kim, S. N., Chen, J.-G., Howell, M., Ried, T., Habermann, J. K., Auer, G., Brenton, J. D., Szallasi, Z., & Downward, J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-05-26
- Volume
- 106
- Issue
- 21
- Pages
- 8671-8676
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2020099456
- Cited by
- 287
- References
- 2
- FWCI
- 7.53
- Type
- journal article
- Language
- en
- Open access
- green
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- Swanton, C., Nicke, B., Schuett, M., Eklund, A. C., Ng, C., Li, Q., Hardcastle, T., Lee, A., Roy, R., East, P., Kschischo, M., Endesfelder, D., Wylie, P., Kim, S. N., Chen, J.-G., Howell, M., Ried, T., Habermann, J. K., Auer, G., . . . Downward, J. (2009). Chromosomal instability determines taxane response. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0811835106
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