Vascular Endothelial Growth Factor Monoclonal Antibody Inhibits Growth of Anaplastic Thyroid Cancer Xenografts in Nude Mice

Abstract

We conclude that systemic VEGF-mAb significantly reduces growth of ATC xenografts and is associated with increased VEGF and p53 expression. Thalidomide has no effect on tumor growth, but is also associated with increased VEGF and p53 expression. These observations provide the first evidence that VEGF-mAb-induced angiogenesis blockade may be of use for the treatment of ATC.

Novel high-affinity PPARγ agonist alone and in combination with paclitaxel inhibits human anaplastic thyroid carcinoma tumor growth via p21WAF1/CIP1

“…VEGF is a potent activator of angiogenesis and is secreted from many tumor types (Panigrahy et al, 2003) including ATC (Belletti et al, 1999;Sato, 2001;Xu et al, 2001). Recently, a VEGF monoclonal antibody recognizing VEGF isoforms 121, 165, and 189 demonstrated antitumor activity against human ARO ATC tumors in a xenograft nude mouse model (Bauer et al, 2002). As well, AEE788, a dual inhibitor of epidermal growth factor receptor (EGFR) and VEGF receptor (VEGFR) tyrosine kinases was able to inhibit the proliferation of ATC cell lines in vitro.…”

Targeting BRAF in thyroid cancer

“…Whether the activity of Sorafenib in thyroid cancer is mediated by inhibiting RAF kinases, RET or its other targets is uncertain. It is of interest that other agents that inhibit VEGF activity specifically have been shown to have salutary effects against thyroid cancer cell lines in vitro and in vivo (Bauer et al, 2003). As described below (see clinical studies section), Sorafenib is currently being evaluated in patients with iodine non-responsive thyroid cancer.…”

Anaplastic thyroid carcinoma

“…In a prospective phase II clinical trial of paclitaxel, 20 patients with metastatic ATC were enrolled and a remarkable response rate of 53% was obtained (Schoenberger et al, 2004). In a preclinical experiment (Schoenberger et al, 2004) only paclitaxel, gemcitabine, and vinorelbine appeared to be active in ATC (Bauer et al, 2003) and the combinations of vinorelbine/gemcitabine and paclitaxel/gemcitabine seemed to act synergistically. These results should receive confirmation in clinical trials.…”

“…A common feature of thyroid cancers is their markedly increased vascularization, with an elevated expression of the vascular endothelial growth factor (VEGF) by immunohistochemistry, compared with normal thyroid tissue (Klein et al, 1999;Bauer et al, 2003). VEGF levels are correlated with stage, tumor size, nodal involvement, extra-thyroidal invasion, and distant metastases (Chaplin et al, 1996).…”

“…Preclinical studies demonstrated that axitinib rapidly and selectively inhibits VEGF-dependent fenestrations and VEGFR-2 and 3 expression in endothelial cells, with the result of blocking angiogenesis and tumor blood flow (Baffert et al, 2006;Kamba et al, 2006;Mancuso et al, 2006;Mooney et al, 2009). The principal mechanism of action of axitinib is inhibition of VEGF signaling (Bauer et al, 2002). …”