The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Transdifferentiation as a Mechanism of Treatment Resistance in a Mouse Model of Castration-Resistant Prostate Cancer
Open accessAbstract
Current treatments for castration-resistant prostate cancer (CRPC) that target androgen receptor (AR) signaling improve patient survival, yet ultimately fail. Here, we provide novel insights into treatment response for the antiandrogen abiraterone by analyses of a genetically engineered mouse (GEM) model with combined inactivation of Trp53 and Pten, which are frequently comutated in human CRPC. These NPp53 mice fail to respond to abiraterone and display accelerated progression to tumors resembling treatment-related CRPC with neuroendocrine differentiation (CRPC-NE) in humans. Cross-species computational analyses identify master regulators of adverse response that are conserved with human CRPC-NE, including the neural differentiation factor SOX11, which promotes neuroendocrine differentiation in cells derived from NPp53 tumors. Furthermore, abiraterone-treated NPp53 prostate tumors contain regions of focal and/or overt neuroendocrine differentiation, distinguished by their proliferative potential. Notably, lineage tracing in vivo provides definitive and quantitative evidence that focal and overt neuroendocrine regions arise by transdifferentiation of luminal adenocarcinoma cells. These findings underscore principal roles for TP53 and PTEN inactivation in abiraterone resistance and progression from adenocarcinoma to CRPC-NE by transdifferentiation. Significance: Understanding adverse treatment response and identifying patients likely to fail treatment represent fundamental clinical challenges. By integrating analyses of GEM models and human clinical data, we provide direct genetic evidence for transdifferentiation as a mechanism of drug resistance as well as for stratifying patients for treatment with antiandrogens. Cancer Discov; 7(7); 736–49. ©2017 AACR. See related commentary by Sinha and Nelson, p. 673. This article is highlighted in the In This Issue feature, p. 653
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Integrative Genomic Profiling of Human Prostate Cancer
Taylor, B. S., Schultz, N., Hieronymus, H., Gopalan, A., Xiao, Y., Carver, B. S., Arora, V. K., Kaushik, P., Cerami, E., Reva, B., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.05.026 · Cited by 3,701
Integrative Clinical Genomics of Advanced Prostate Cancer
Robinson, D., Van Allen, E. M., Wu, Y.-M., Schultz, N., Lonigro, R. J., Mosquera, J.-M., Montgomery, B., Taplin, M.-E., Pritchard, C. C., Attard, G., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.001 · Cited by 3,645
Self-citationGenotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors
Sequist, L. V., Waltman, B. A., Dias-Santagata, D., Digumarthy, S., Turke, A. B., Fidias, P., Bergethon, K., Shaw, A. T., Gettinger, S., Cosper, A. K., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002003 · Cited by 3,499
The Molecular Taxonomy of Primary Prostate Cancer
Abeshouse, A., Ahn, J., Akbani, R., Ally, A., Amin, S., Andry, C. D., Annala, M., Aprikian, A., Armenia, J., Arora, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.10.025 · Cited by 3,110
Self-citationThe mutational landscape of lethal castration-resistant prostate cancer
Grasso, C. S., Wu, Y.-M., Robinson, D. R., Cao, X., Dhanasekaran, S. M., Khan, A. P., Quist, M. J., Jing, X., Lonigro, R. J., Brenner, J. C., et al. (2012) · Nature · doi:10.1038/nature11125 · Cited by 2,517
Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis
Chen, Z., Trotman, L. C., Shaffer, D., Lin, H.-K., Dotan, Z. A., Niki, M., Koutcher, J. A., Scher, H. I., Ludwig, T., Gerald, W., et al. (2005) · Nature · doi:10.1038/nature03918 · Cited by 1,993
Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer
Beltran, H., Prandi, D., Mosquera, J. M., Benelli, M., Puca, L., Cyrta, J., Marotz, C., Giannopoulou, E., Chakravarthi, B. V. S. K., Varambally, S., et al. (2016) · Nature Medicine · doi:10.1038/nm.4045 · Cited by 1,685
Self-citationExome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer
Barbieri, C. E., Baca, S. C., Lawrence, M. S., Demichelis, F., Blattner, M., Theurillat, J.-P., White, T. A., Stojanov, P., Van Allen, E., Stransky, N., et al. (2012) · Nature Genetics · doi:10.1038/ng.2279 · Cited by 1,558
Self-citationEmerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer
Watson, P. A., Arora, V. K., & Sawyers, C. L. (2015) · Nature Reviews Cancer · doi:10.1038/nrc4016 · Cited by 1,536
Punctuated Evolution of Prostate Cancer Genomes
Baca, S. C., Prandi, D., Lawrence, M. S., Mosquera, J. M., Romanel, A., Drier, Y., Park, K., Kitabayashi, N., MacDonald, T. Y., Ghandi, M., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.021 · Cited by 1,320
Self-citation
Cited by
Androgen Receptor Pathway-Independent Prostate Cancer Is Sustained through FGF Signaling
Bluemn, E. G., Coleman, I. M., Lucas, J. M., Coleman, R. T., Hernandez-Lopez, S., Tharakan, R., Bianchi-Frias, D., Dumpit, R. F., Kaipainen, A., Corella, A. N., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.09.003 · Cited by 744
Self-citationLineage 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
Cellular plasticity and the neuroendocrine phenotype in prostate cancer
Davies, A. H., Beltran, H., & Zoubeidi, A. (2018) · Nature Reviews Urology · doi:10.1038/nrurol.2018.22 · Cited by 431
Persistent Cancer Cells: The Deadly Survivors
Shen, S., Vagner, S., & Robert, C. (2020) · Cell · doi:10.1016/j.cell.2020.10.027 · Cited by 304
Emerging role of tumor cell plasticity in modifying therapeutic response
Qin, S., Jiang, J., Lu, Y., Nice, E. C., Huang, C., Zhang, J., & He, W. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00313-5 · Cited by 268
Metadata
- Authors
- Zou, M., Toivanen, R., Mitrofanova, A., Floch, N., Hayati, S., Sun, Y., Le Magnen, C., Chester, D., Mostaghel, E. A., Califano, A., Rubin, M. A., Shen, M. M., & Abate-Shen, C.
- Venue
- Cancer Discovery
- Published
- 2017-07-01
- Volume
- 7
- Issue
- 7
- Pages
- 736-749
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2607041430
- Cited by
- 386
- References
- 58
- FWCI
- 28.35
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Transdifferentiation as a Mechanism of Treatment Resistance in a Mouse Model of Castration-Resistant Prostate Cancer. https://app.cochat.ai/papers/10.1158/2159-8290.cd-16-1174
- The paper
- Zou, M., Toivanen, R., Mitrofanova, A., Floch, N., Hayati, S., Sun, Y., Le Magnen, C., Chester, D., Mostaghel, E. A., Califano, A., Rubin, M. A., Shen, M. M., & Abate-Shen, C. (2017). Transdifferentiation as a Mechanism of Treatment Resistance in a Mouse Model of Castration-Resistant Prostate Cancer. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-16-1174
Data sources
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.
