The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
LY2109761, a novel transforming growth factor β receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis
Open accessAbstract
Most pancreatic cancer patients present with inoperable disease or develop metastases after surgery. Conventional therapies are usually ineffective in treating metastatic disease. It is evident that novel therapies remain to be developed. Transforming growth factor β (TGF-β) plays a key role in cancer metastasis, signaling through the TGF-β type I/II receptors (TβRI/II). We hypothesized that targeting TβRI/II kinase activity with the novel inhibitor LY2109761 would suppress pancreatic cancer metastatic processes. The effect of LY2109761 has been evaluated on soft agar growth, migration, invasion using a fibroblast coculture model, and detachment-induced apoptosis (anoikis) by Annexin V flow cytometric analysis. The efficacy of LY2109761 on tumor growth, survival, and reduction of spontaneous metastasis have been evaluated in an orthotopic murine model of metastatic pancreatic cancer expressing both luciferase and green fluorescence proteins (L3.6pl/GLT). To determine whether pancreatic cancer cells or the cells in the liver microenvironment were involved in LY2109761-mediated reduction of liver metastasis, we used a model of experimental liver metastasis. LY2109761 significantly inhibited the L3.6pl/GLT soft agar growth, suppressed both basal and TGF-β1−induced cell migration and invasion, and induced anoikis. In vivo, LY2109761, in combination with gemcitabine, significantly reduced the tumor burden, prolonged survival, and reduced spontaneous abdominal metastases. Results from the experimental liver metastasis models indicate an important role for targeting TβRI/II kinase activity on tumor and liver microenvironment cells in suppressing liver metastasis. Targeting TβRI/II kinase activity on pancreatic cancer cells or the cells of the liver microenvironment represents a novel therapeutic approach to prevent pancreatic cancer metastasis. [Mol Cancer Ther 2008;7(4):829–40]
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Cites
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Cited by
Olive, K. P., Jacobetz, M. A., Davidson, C. J., Gopinathan, A., McIntyre, D., Honess, D., Madhu, B., Goldgraben, M. A., Caldwell, M. E., Allard, D., et al. (2009) · Science · doi:10.1126/science.1171362 · Cited by 3,170
Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver
Costa-Silva, B., Aiello, N. M., Ocean, A. J., Singh, S., Zhang, H., Thakur, B. K., Becker, A., Hoshino, A., Mark, M. T., Molina, H., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3169 · Cited by 2,692
Targeting the TGFβ signalling pathway in disease
Akhurst, R. J., & Hata, A. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3810 · Cited by 1,466
Extracellular matrix and its therapeutic potential for cancer treatment
Huang, J., Zhang, L., Wan, D., Zhou, L., Zheng, S., Lin, S., & Qiao, Y. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00544-0 · Cited by 962
The polarization of immune cells in the tumour environment by TGFβ
Flavell, R. A., Sanjabi, S., Wrzesinski, S. H., & Licona-Limón, P. (2010) · Nature Reviews Immunology · doi:10.1038/nri2808 · Cited by 940
Metadata
- Authors
- Melisi, D., Ishiyama, S., Sclabas, G. M., Fleming, J. B., Xia, Q., Tortora, G., Abbruzzese, J. L., & Chiao, P. J.
- Venue
- Molecular Cancer Therapeutics
- Published
- 2008-04-01
- Volume
- 7
- Issue
- 4
- Pages
- 829-840
- ISSN
- 1535-7163 (ISSN-L)
- 1538-8514
- OpenAlex
- W1974423029
- Cited by
- 323
- References
- 4
- FWCI
- 4.96
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Melisi, D., Ishiyama, S., Sclabas, G. M., Fleming, J. B., Xia, Q., Tortora, G., Abbruzzese, J. L., & Chiao, P. J. (2008). LY2109761, a novel transforming growth factor β receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis. Molecular Cancer Therapeutics. https://doi.org/10.1158/1535-7163.mct-07-0337
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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