Artículo

Wan, X.; Corn, P.G.; Yang, J.; Palanisamy, N.; Starbuck, M.W.; Efstathiou, E.; Li-Ning Tapia, E.M.; Zurita, A.J.; Aparicio, A.; Ravoori, M.K.; Vazquez, E.S.; Robinson, D.R.; Wu, Y.-M.; Cao, X.; Iyer, M.K.; McKeehan, W.; Kundra, V.; Wang, F. (...) Navone, N.M. "Prostate cancer cell-stromal cell crosstalk via FGFR1 mediates antitumor activity of dovitinib in bone metastases" (2014) Science Translational Medicine. 6(252)
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Abstract:

Bone is the most common site of prostate cancer (PCa) progression to a therapy-resistant, lethal phenotype. We found that blockade of fibroblast growth factor receptors (FGFRs) with the receptor tyrosine kinase inhibitor dovitinib has clinical activity in a subset of men with castration-resistant PCa and bone metastases. Our integrated analyses suggest that FGF signaling mediates a positive feedback loop between PCa cells and bone cells and that blockade of FGFR1 in osteoblasts partially mediates the antitumor activity of dovitinib by improving bone quality and by blocking PCa cell-bone cell interaction. These findings account for clinical observations such as reductions in lesion size and intensity on bone scans, lymph node size, and tumor-specific symptoms without proportional declines in serum prostate-specific antigen concentration. Our findings suggest that targeting FGFR has therapeutic activity in advanced PCa and provide direction for the development of therapies with FGFR inhibitors. © 2014, American Association for the Advancement of Science. All rights reserved.

Registro:

Documento: Artículo
Título:Prostate cancer cell-stromal cell crosstalk via FGFR1 mediates antitumor activity of dovitinib in bone metastases
Autor:Wan, X.; Corn, P.G.; Yang, J.; Palanisamy, N.; Starbuck, M.W.; Efstathiou, E.; Li-Ning Tapia, E.M.; Zurita, A.J.; Aparicio, A.; Ravoori, M.K.; Vazquez, E.S.; Robinson, D.R.; Wu, Y.-M.; Cao, X.; Iyer, M.K.; McKeehan, W.; Kundra, V.; Wang, F.; Troncoso, P.; Chinnaiyan, A.M.; Logothetis, C.J.; Navone, N.M.
Filiación:Department of Genitourinary Medical Oncology, David H. Koch Center for Applied Research of Genitourinary Cancers, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, United States
Rolanette and Berdon Lawrence Bone Disease Program of Texas, Houston, TX 77030, United States
University of Athens Greece School of Medicine, Athens, 11528, Greece
Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
Department of Biological Chemistry, University of Buenos Aires-National Research Council of Argentina (CONICET-IQUIBICEN), Ciudad Autonoma de Buenos Aires, C1428EGA, Argentina
Center for Cancer and Stem Cell Biology, IBT-Texas AandM Health Science Center, Houston, TX 77030, United States
Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
Palabras clave:dovitinib; fibroblast growth factor; fibroblast growth factor receptor 1; prostate specific antigen; 4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; antineoplastic agent; benzimidazole derivative; fibroblast growth factor 2; fibroblast growth factor receptor 1; quinolone derivative; animal experiment; animal model; antiangiogenic activity; antineoplastic activity; Article; bone metastasis; bone quality; bone scintiscanning; cancer cell; castration resistant prostate cancer; cell interaction; controlled study; drug megadose; drug targeting; human; human cell; low drug dose; lymph node; lymph node size; molecular interaction; mouse; musculoskeletal system parameters; nonhuman; osteoblast; positive feedback; prostate cancer; protein blood level; protein expression; receptor blocking; signal transduction; stroma cell; tumor microenvironment; tumor volume; animal; apoptosis; bone; Bone Neoplasms; disease model; drug effects; drug screening; gene expression regulation; genetics; male; metabolism; Neovascularization, Pathologic; pathology; Prostatic Neoplasms; secondary; stroma cell; tumor cell line; vascularization; Animals; Antineoplastic Agents; Apoptosis; Benzimidazoles; Bone and Bones; Bone Neoplasms; Cell Line, Tumor; Disease Models, Animal; Fibroblast Growth Factor 2; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Neovascularization, Pathologic; Osteoblasts; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Quinolones; Receptor, Fibroblast Growth Factor, Type 1; Signal Transduction; Stromal Cells; Tumor Microenvironment; Xenograft Model Antitumor Assays
Año:2014
Volumen:6
Número:252
DOI: http://dx.doi.org/10.1126/scitranslmed.3009332
Título revista:Science Translational Medicine
Título revista abreviado:Sci. Transl. Med.
ISSN:19466234
CAS:dovitinib, 804551-71-1, 915769-50-5; fibroblast growth factor, 62031-54-3; fibroblast growth factor 2, 106096-93-9; 4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; Antineoplastic Agents; Benzimidazoles; Fibroblast Growth Factor 2; Quinolones; Receptor, Fibroblast Growth Factor, Type 1
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19466234_v6_n252_p_Wan

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Citas:

---------- APA ----------
Wan, X., Corn, P.G., Yang, J., Palanisamy, N., Starbuck, M.W., Efstathiou, E., Li-Ning Tapia, E.M.,..., Navone, N.M. (2014) . Prostate cancer cell-stromal cell crosstalk via FGFR1 mediates antitumor activity of dovitinib in bone metastases. Science Translational Medicine, 6(252).
http://dx.doi.org/10.1126/scitranslmed.3009332
---------- CHICAGO ----------
Wan, X., Corn, P.G., Yang, J., Palanisamy, N., Starbuck, M.W., Efstathiou, E., et al. "Prostate cancer cell-stromal cell crosstalk via FGFR1 mediates antitumor activity of dovitinib in bone metastases" . Science Translational Medicine 6, no. 252 (2014).
http://dx.doi.org/10.1126/scitranslmed.3009332
---------- MLA ----------
Wan, X., Corn, P.G., Yang, J., Palanisamy, N., Starbuck, M.W., Efstathiou, E., et al. "Prostate cancer cell-stromal cell crosstalk via FGFR1 mediates antitumor activity of dovitinib in bone metastases" . Science Translational Medicine, vol. 6, no. 252, 2014.
http://dx.doi.org/10.1126/scitranslmed.3009332
---------- VANCOUVER ----------
Wan, X., Corn, P.G., Yang, J., Palanisamy, N., Starbuck, M.W., Efstathiou, E., et al. Prostate cancer cell-stromal cell crosstalk via FGFR1 mediates antitumor activity of dovitinib in bone metastases. Sci. Transl. Med. 2014;6(252).
http://dx.doi.org/10.1126/scitranslmed.3009332