The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer
Open accessAbstract
An increasingly recognized resistance mechanism to androgen receptor (AR)-directed therapy in prostate cancer involves epithelial plasticity, in which tumor cells demonstrate low to absent AR expression and often have neuroendocrine features. The etiology and molecular basis for this 'alternative' treatment-resistant cell state remain incompletely understood. Here, by analyzing whole-exome sequencing data of metastatic biopsies from patients, we observed substantial genomic overlap between castration-resistant tumors that were histologically characterized as prostate adenocarcinomas (CRPC-Adeno) and neuroendocrine prostate cancer (CRPC-NE); analysis of biopsy samples from the same individuals over time points to a model most consistent with divergent clonal evolution. Genome-wide DNA methylation analysis revealed marked epigenetic differences between CRPC-NE tumors and CRPC-Adeno, and also designated samples of CRPC-Adeno with clinical features of AR independence as CRPC-NE, suggesting that epigenetic modifiers may play a role in the induction and/or maintenance of this treatment-resistant state. This study supports the emergence of an alternative, 'AR-indifferent' cell state through divergent clonal evolution as a mechanism of treatment resistance in advanced prostate cancer.
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
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
Cerami, E., Gao, J., Dogrusoz, U., Gross, B. E., Sumer, S. O., Aksoy, B. A., Jacobsen, A., Byrne, C. J., Heuer, M. L., Larsson, E., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0095 · Cited by 17,455
Comprehensive molecular characterization of human colon and rectal cancer
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11252 · Cited by 8,499
Nowell, P. C. (1976) · Science · doi:10.1126/science.959840 · Cited by 6,471
Mutational heterogeneity in cancer and the search for new cancer-associated genes
Lawrence, M. S., Stojanov, P., Polak, P., Kryukov, G. V., Cibulskis, K., Sivachenko, A., Carter, S. L., Stewart, C., Mermel, C. H., Roberts, S. A., et al. (2013) · Nature · doi:10.1038/nature12213 · Cited by 5,461
Self-citationAbiraterone and Increased Survival in Metastatic Prostate Cancer
de Bono, J. S., Logothetis, C. J., Molina, A., Fizazi, K., North, S., Chu, L., Chi, K. N., Jones, R. J., Goodman, O. B., Saad, F., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1014618 · Cited by 4,407
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-citationAR-V7 and Resistance to Enzalutamide and Abiraterone in Prostate Cancer
Antonarakis, E. S., Lu, C., Wang, H., Luber, B., Nakazawa, M., Roeser, J. C., Chen, Y., Mohammad, T. A., Chen, Y., Fedor, H. L., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1315815 · Cited by 2,710
The 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
Self-citationMolecular determinants of resistance to antiandrogen therapy
Chen, C. D., Welsbie, D. S., Tran, C., Baek, S. H., Chen, R., Vessella, R., Rosenfeld, M. G., & Sawyers, C. L. (2004) · Nature Medicine · doi:10.1038/nm972 · Cited by 2,278
Cited by
Genomic correlates of clinical outcome in advanced prostate cancer
Abida, W., Cyrta, J., Heller, G., Prandi, D., Armenia, J., Coleman, I., Cieslik, M., Benelli, M., Robinson, D., Van Allen, E. M., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1902651116 · Cited by 1,372
Self-citationMu, P., Zhang, Z., Benelli, M., Karthaus, W. R., Hoover, E., Chen, C.-C., Wongvipat, J., Ku, S.-Y., Gao, D., Cao, Z., et al. (2017) · Science · doi:10.1126/science.aah4307 · Cited by 1,050
Self-citationAggarwal, R., Huang, J., Alumkal, J. J., Zhang, L., Feng, F. Y., Thomas, G. V., Weinstein, A. S., Friedl, V., Zhang, C., Witte, O. N., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.77.6880 · Cited by 810
Self-citationAndrogen 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
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
A Convergence-Based Framework for Cancer Drug Resistance
Konieczkowski, D. J., Johannessen, C. M., & Garraway, L. A. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.025 · Cited by 258
Self-citationDelta-like protein 3 expression and therapeutic targeting in neuroendocrine prostate cancer
Puca, L., Gavyert, K., Sailer, V., Conteduca, V., Dardenne, E., Sigouros, M., Isse, K., Kearney, M., Vosoughi, A., Fernandez, L., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aav0891 · Cited by 214
Self-citationMolecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer
Gu, Y., Yang, R., Zhang, Y., Guo, M., Takehiro, K., Zhan, M., Yang, L., & Wang, H. (2025) · Molecular Biomedicine · doi:10.1186/s43556-024-00239-2 · Cited by 184
FOXA2 drives lineage plasticity and KIT pathway activation in neuroendocrine prostate cancer
Han, M., Li, F., Zhang, Y., Dai, P., He, J., Li, Y., Zhu, Y., Zheng, J., Huang, H., Bai, F., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.10.011 · Cited by 166
Henzler, C., Li, Y., Yang, R., McBride, T., Ho, Y., Sprenger, C., Liu, G., Coleman, I., Lakely, B., Li, R., et al. (2016) · Nature Communications · doi:10.1038/ncomms13668 · Cited by 173
Carabet, L. A., Rennie, P. S., & Cherkasov, A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms20010120 · Cited by 172
Biological determinants of PSMA expression, regulation and heterogeneity in prostate cancer
Bakht, M. K., & Beltran, H. (2025) · Nature Reviews Urology · doi:10.1038/s41585-024-00900-z · Cited by 158
Self-citationIntegrative epigenetic taxonomy of primary prostate cancer
Stelloo, S., Nevedomskaya, E., Kim, Y., Schuurman, K., Valle-Encinas, E., Lobo, J., Krijgsman, O., Peeper, D. S., Chang, S. L., Feng, F. Y.-C., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07270-2 · Cited by 154
Trop2 is a driver of metastatic prostate cancer with neuroendocrine phenotype via PARP1
Hsu, E.-C., Rice, M. A., Bermudez, A., Marques, F. J. G., Aslan, M., Liu, S., Ghoochani, A., Zhang, C. A., Chen, Y.-S., Zlitni, A., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1905384117 · Cited by 146
Targeting CD46 for both adenocarcinoma and neuroendocrine prostate cancer
Su, Y., Liu, Y., Behrens, C. R., Bidlingmaier, S., Lee, N.-K., Aggarwal, R., Sherbenou, D. W., Burlingame, A. L., Hann, B. C., Simko, J. P., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.121497 · Cited by 82
Ruiz de Porras, V., Font, A., & Aytes, A. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.08.033 · Cited by 65
Joshi, M., Kim, J., D’Alessandro, A., Monk, E., Bruce, K., Elajaili, H., Nozik-Grayck, E., Goodspeed, A., Costello, J. C., & Schlaepfer, I. R. (2020) · Cancers · doi:10.3390/cancers12113431 · Cited by 54
Drabovich, A. P., Saraon, P., Drabovich, M., Karakosta, T. D., Dimitromanolakis, A., Hyndman, M. E., Jarvi, K., & Diamandis, E. P. (2019) · Molecular & Cellular Proteomics · doi:10.1074/mcp.ra119.001612 · Cited by 40
Das, R., Sjöström, M., Shrestha, R., Yogodzinski, C., Egusa, E. A., Chesner, L. N., Chen, W. S., Chou, J., Dang, D. K., Swinderman, J. T., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24919-7 · Cited by 38
Hwang, J. H., Arafeh, R., Seo, J.-H., Baca, S. C., Ludwig, M., Arnoff, T. E., Sawyer, L., Richter, C., Tape, S., Bergom, H. E., et al. (2022) · eLife · doi:10.7554/elife.73223 · Cited by 26
Self-citationUnraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts
Sychev, Z. E., Day, A., Bergom, H. E., Larson, G., Ali, A., Ludwig, M., Boytim, E., Coleman, I., Corey, E., Plymate, S. R., et al. (2024) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-23-0976 · Cited by 13
Hwang, J., Likasitwatanakul, P., Deshmukh, S. K., Wu, S., Kwon, J. J., Toye, E., Moline, D., Evans, M. G., Elliott, A., Passow, R., et al. (2025) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-24-3471 · Cited by 12
Therapy-Induced Transdifferentiation Promotes Glioma Growth Independent of EGFR Signaling
Oh, H., Hwang, I., Jang, J.-Y., Wu, L., Cao, D., Yao, J., Ying, H., Li, J. Y., Yao, Y., Hu, B., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-1810 · Cited by 11
Metadata
- Authors
- Beltran, H., Prandi, D., Mosquera, J. M., Benelli, M., Puca, L., Cyrta, J., Marotz, C., Giannopoulou, E., Chakravarthi, B. V. S. K., Varambally, S., Tomlins, S. A., Nanus, D. M., Tagawa, S. T., Van Allen, E. M., Elemento, O., Sboner, A., Garraway, L. A., Rubin, M. A., & Demichelis, F.
- Venue
- Nature Medicine
- Published
- 2016-02-08
- Volume
- 22
- Issue
- 3
- Pages
- 298-305
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2262087934
- Cited by
- 1,685
- References
- 11
- FWCI
- 130.03
- 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
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.
