The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974
Open accessAbstract
Significance: Targeting the Wnt pathway in cancer is an attractive therapeutic approach. However, success has been limited because of the lack of effective therapeutic agents and the lack of biomarkers to define the patient population that would benefit from such a therapy. Herein, we report the discovery of LGK974, a drug that targets Porcupine, a Wnt-specific acyltransferase. We show that LGK974 potently inhibits Wnt signaling, has strong efficacy in rodent tumor models, and is well-tolerated. We also show that head and neck cancer cell lines with loss-of-function mutations in the Notch signaling pathway have a high response rate to LGK974. Together, these findings provide a strategy and tools for targeting Wnt-driven cancer.
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Citations
Cites
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Lgr5+ve Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units In Vitro
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Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors
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ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner
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Notch1 functions as a tumor suppressor in mouse skin
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“Affected individuals s with aberrations in RNF43, ZNRF3, or RSPO2 (overall 6% of affected individuals) are predicted to respond to porcupine inhibitors (Liu et al., 2013).”
The multifaceted roles of fatty acid synthesis in cancer
Röhrig, F., & Schulze, A. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.89 · Cited by 1,651
Tackling the cancer stem cells — what challenges do they pose?
Pattabiraman, D. R., & Weinberg, R. A. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4253 · Cited by 990
Opportunities and challenges in phenotypic drug discovery: an industry perspective
Moffat, J. G., Vincent, F., Lee, J. A., Eder, J., & Prunotto, M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.111 · Cited by 939
Oral squamous cell carcinomas: state of the field and emerging directions
Tan, Y., Wang, Z., Xu, M., Li, B., Huang, Z., Qin, S., Nice, E. C., Tang, J., & Huang, C. (2023) · International Journal of Oral Science · doi:10.1038/s41368-023-00249-w · Cited by 831
Metadata
- Authors
- Liu, J., Pan, S., Hsieh, M. H., Ng, N., Sun, F., Wang, T., Kasibhatla, S., Schuller, A. G., Li, A. G., Cheng, D., Li, J., Tompkins, C., Pferdekamper, A., Steffy, A., Cheng, J., Kowal, C., Phung, V., Guo, G., Wang, Y., Graham, M. P., Flynn, S., Brenner, J. C., Li, C., Villarroel, M. C., Schultz, P. G., Wu, X., McNamara, P., Sellers, W. R., Petruzzelli, L., Boral, A. L., Seidel, H. M., McLaughlin, M. E., Che, J., Carey, T. E., Vanasse, G., & Harris, J. L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2013-11-25
- Volume
- 110
- Issue
- 50
- Pages
- 20224-20229
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1994029539
- Cited by
- 831
- References
- 46
- FWCI
- 22.86
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Liu, J., Pan, S., Hsieh, M. H., Ng, N., Sun, F., Wang, T., Kasibhatla, S., Schuller, A. G., Li, A. G., Cheng, D., Li, J., Tompkins, C., Pferdekamper, A., Steffy, A., Cheng, J., Kowal, C., Phung, V., Guo, G., Wang, Y., . . . Harris, J. L. (2013). Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1314239110
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