Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors
Citations
3,486 citations
Cites background from "Drug resistance by evasion of antia..."
...…is likely multifactorial, based on preclinical studies in mouse models, which have revealed in some cases evasion of the signaling blockage (Casanovas et al., 2005), in others recruitment of additional or different subtypes of proangiogenic IICs or CAFs (Priceman et al., 2010; Shojaei et…...
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2,670 citations
2,303 citations
Cites background or methods from "Drug resistance by evasion of antia..."
...Therapeutic Trials RIP1-Tag2 mice were treated starting at 10 or 12 weeks of age as indicated, and immunocompromised RIP1-Tag2;Rag1-KO mice were used for longterm DC101 treatment to avoid immune reaction against the therapeutic antibody....
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...Tumor-bearing immunocompromised RIP1-Tag2 mice treated with DC101 for a relatively brief period of 1 week had reduced tumor vasculature and volume compared to control age-matched untreated animals, as described previously (Figure 1A and data not shown; Casanovas et al., 2005)....
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...This realization motivates clinical studies to confirm and potentially target this insidious consequence of antiangiogenic therapies. growth factor (FGF) ligands (Casanovas et al., 2005)....
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...…were used: (1) 1 mg/mouse twice per week of anti-VEGFR2 blocking antibody (DC101) purified from a hybridoma culture (American Type Culture Collection) and its control purified rat IgG (Jackson ImmunoResearch) as described previously (Casanovas et al., 2005) administered intraperitoneally (i.p.)....
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...Error bars indicate ± SD. VEGFR2 (DC101) in the RIP1-Tag2 model of pancreatic neuroendocrine cancer (PNET) (Casanovas et al., 2005), we sought to focus on the initial onset of malignant progression to invasive islet carcinoma....
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2,211 citations
Cites background from "Drug resistance by evasion of antia..."
...Finally there is substantial crosstalk between FGFR and vascular endothelial growth factor receptor (VEGFR) signalling in angiogenesis, and the FGFR system may mediate resistance to VEGFR targeting in some situation...
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2,192 citations
Additional excerpts
...Constipation 12 (14) 12 (14) 0 16 (20) 15 (18) 1 (1)...
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References
10,161 citations
"Drug resistance by evasion of antia..." refers background or result in this paper
...…bevacizumab (Avastin), a humanized monoclonal antibody against VEGF-A, in combination with conventional chemotherapy, increased CANCER CELL : OCTOBER 2005 · VOL. 8 · COPYRIGHT © 2005 ELSEVIER overall survival by 5 months in colorectal cancer patients (Hurwitz et al., 2004), leading to FDA approval....
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...To date, human clinical trials that selectively target VEGF or VEGFRs are merely delaying time to progression after a period of stable disease, thus CANCER CELL : OCTOBER 2005 affording a modest survival advantage (e.g., Hurwitz et al., 2004), much like that seen in this mouse model of cancer....
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...This pattern of tumor stasis and then tumor growth is arguably analogous to the delayed time to progression seen in the clinical trials with bevacizumab (Avastin) as monotherapy (Yang et al., 2003) or in combination with chemotherapy (Hurwitz et al., 2004)....
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8,942 citations
"Drug resistance by evasion of antia..." refers background in this paper
...A prominent proangiogenic signaling circuit involves the vascular endothelial growth factor (VEGF) family, and in particular VEGF-A (Ferrara et al., 2003)....
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...A recent phase III clinical trial demonstrated that bevacizumab (Avastin), a humanized monoclonal antibody against VEGF-A, in combination with conventional chemotherapy, increased CANCER CELL : OCTOBER 2005 · VOL. 8 · COPYRIGHT © 2005 ELSEVIER overall survival by 5 months in colorectal cancer patients (Hurwitz et al., 2004), leading to FDA approval....
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...Here, we use specific function-blocking monoclonal antibodies to two VEGF receptors to probe their role in mediating and sustaining angiogenesis and tumor growth in an endogenous mouse model of islet cell carcinogenesis, where the functional importance of VEGF signaling has been previously documented, via gene knockout of VEGF-A (Inoue et al., 2002) and pharmacological inhibition of VEGF receptors with small molecules (Bergers et al., 2000, 2003)....
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...While the VEGF-A ligand is itself upregulated in the treated tumors (and hypoxic tumor cell lines), it is evidently in- CANCER CELL : OCTOBER 2005 Figure 6....
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...Using mRNA prepared from these two FACS-purified cell populations, we evaluated the expression levels of the proangiogenic ligands and found that most were upregulated in the tumor cell population (VEGF-A, FGF1, FGF2, FGF7, FGF8, Ephrin-A1, and Angiopoietin-2) whereas a partially overlapping set was upregulated in the tumor endothelial cells (FGF1, FGF2, Ephrin-A1, and Angiopoietin-1 and -2) (Figure 5B)....
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6,895 citations
"Drug resistance by evasion of antia..." refers background in this paper
...…balance shifts in favor of angiogenesis inducers, an angiogenic switch activates the normally quiescent vasculature to develop new blood vessels (Hanahan and Folkman, 1996), often concomitant with enlargement (dilation and microhemorrhaging) of the preexisting vasculature (Ryschich et al.,…...
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2,821 citations
"Drug resistance by evasion of antia..." refers background in this paper
...(Hanahan, 1985) and the Rag1 knockout (Mombaerts et al., 1992) have...
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...The generation and characterization of the single transgenic RIP-Tag2 mice (Hanahan, 1985) and the Rag1 knockout (Mombaerts et al., 1992) have been previously reported....
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...Mice lacking Rag1 are unable to perform V(D)J recombination of immunoglobulins and T cell receptor genes during immune cell maturation, and thus are completely deficient in adaptive immunity (Mombaerts et al., 1992)....
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2,724 citations
"Drug resistance by evasion of antia..." refers result in this paper
...This pattern of tumor stasis and then tumor growth is arguably analogous to the delayed time to progression seen in the clinical trials with bevacizumab (Avastin) as monotherapy (Yang et al., 2003) or in combination with chemotherapy (Hurwitz et al....
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...This pattern of tumor stasis and then tumor growth is arguably analogous to the delayed time to progression seen in the clinical trials with bevacizumab (Avastin) as monotherapy (Yang et al., 2003) or in combination with chemotherapy (Hurwitz et al., 2004)....
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