Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...

Details

Autor(en) / Beteiligte
Titel
FAK regulates platelet extravasation and tumor growth after antiangiogenic therapy withdrawal
Ist Teil von
  • The Journal of clinical investigation, 2016-05, Vol.126 (5), p.1885-1896
Ort / Verlag
United States: American Society for Clinical Investigation
Erscheinungsjahr
2016
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
  • Recent studies in patients with ovarian cancer suggest that tumor growth may be accelerated following cessation of antiangiogenesis therapy; however, the underlying mechanisms are not well understood. In this study, we aimed to compare the effects of therapy withdrawal to those of continuous treatment with various antiangiogenic agents. Cessation of therapy with pazopanib, bevacizumab, and the human and murine anti-VEGF antibody B20 was associated with substantial tumor growth in mouse models of ovarian cancer. Increased tumor growth was accompanied by tumor hypoxia, increased tumor angiogenesis, and vascular leakage. Moreover, we found hypoxia-induced ADP production and platelet infiltration into tumors after withdrawal of antiangiogenic therapy, and lowering platelet counts markedly inhibited tumor rebound after withdrawal of antiangiogenic therapy. Focal adhesion kinase (FAK) in platelets regulated their migration into the tumor microenvironment, and FAK-deficient platelets completely prevented the rebound tumor growth. Additionally, combined therapy with a FAK inhibitor and the antiangiogenic agents pazopanib and bevacizumab reduced tumor growth and inhibited negative effects following withdrawal of antiangiogenic therapy. In summary, these results suggest that FAK may be a unique target in situations in which antiangiogenic agents are withdrawn, and dual targeting of FAK and VEGF could have therapeutic implications for ovarian cancer management.
Sprache
Englisch
Identifikatoren
ISSN: 0021-9738, 1558-8238
eISSN: 1558-8238
DOI: 10.1172/JCI85086
Titel-ID: cdi_proquest_miscellaneous_1787087283
Format
Schlagworte
Adenosine Diphosphate - metabolism, Analysis, Animals, Antiangiogenesis Therapy, Antibodies, Neoplasm - pharmacology, Antimitotic agents, Antineoplastic agents, Antineoplastic Combined Chemotherapy Protocols - pharmacology, basic medicine, Bevacizumab, Bevacizumab - pharmacology, Biomedical research, Blood Platelets - pathology, Cancer research, Cancer therapies, Care and treatment, Cell culture, Cell Hypoxia - drug effects, Cell Hypoxia - genetics, Cell Line, Tumor, clinical medicine, Clinical trials, Cytokines, Development and progression, developmental biology, Disease prevention, Dosage and administration, Endocrinology, Experiments, Extravasation, Female, Focal Adhesion Kinase 1 - antagonists & inhibitors, Focal Adhesion Kinase 1 - genetics, Focal Adhesion Kinase 1 - metabolism, Grants, Health aspects, Humans, Hypoxia, Internal medicine, medical and health sciences, Medical research, Metastasis, Mice, Mice, Knockout, Microscopy, Neoplasm Proteins - antagonists & inhibitors, Neoplasm Proteins - genetics, Neoplasm Proteins - metabolism, Neovascularization, Neovascularization, Pathologic - drug therapy, Neovascularization, Pathologic - enzymology, Neovascularization, Pathologic - genetics, Neovascularization, Pathologic - pathology, oncology & carcinogenesis, Ovarian cancer, Ovarian Neoplasms - drug therapy, Ovarian Neoplasms - enzymology, Ovarian Neoplasms - genetics, Ovarian Neoplasms - pathology, Pazopanib, Pyrimidines - pharmacology, Studies, Sulfonamides - pharmacology, Tumor hypoxia, Tumor microenvironment, Tumor Microenvironment - drug effects, Tumor Microenvironment - genetics, Tumors, Vascular endothelial growth factor, Xenograft Model Antitumor Assays

Weiterführende Literatur

Empfehlungen zum selben Thema automatisch vorgeschlagen von bX