Colorectal cancer and antiangiogenic therapy: What can be expected in clinical practice?

Mancuso, Andrea; Sternberg, Cora N.

doi:10.1016/j.critrevonc.2005.03.005

Cited by 24 publications

(18 citation statements)

References 97 publications

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“…As a matter of fact, colorectal cancer is one of the best-studied models of tumor angiogenesis (74). As in many other tumors, several angiogenic regulators have been recognized in colon cancer, including VEGF, PDGF, thrombospondin, and angiopoietins (74,75). Likewise, overexpression of FGF and FGFRs in colon cancer cells and tissues, as well as increase of FGF-2 serum levels in patients with advanced colon cancer, have been extensively reported (76)(77)(78)(79)(80)(81).…”

Section: Angiogenesis In Gastrointestinal Cancersmentioning

confidence: 99%

The Angiogenic Switch Molecule, Secreted FGF-Binding Protein, an Indicator of Early Stages of Pancreatic and Colorectal Adenocarcinoma

Tassi

Wellstein

2006

Seminars in Oncology

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Tumor angiogenesis has been related to the initiation as well as progression toward more aggressive behavior of human tumors. We will discuss genetic events underlying the initiation and progression of colorectal and pancreatic adenocarcinoma with a particular focus on the modulation of angiogenesis. A secreted fibroblast growth factor (FGF) binding protein (FGF-BP), which is an extracellular chaperone molecule for FGFs, has been shown to enhance FGF-mediated biochemical and biologic events and to be a crucial rate-limiting factor for tumor-dependent angiogenesis. Histochemical and in situ hybridization studies with archival samples show that FGF-BP is induced early during the initiation of colorectal and pancreatic adenocarcinoma. We will discuss the potential of this secreted protein as a serum marker to identify at-risk subjects.

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Section: Angiogenesis In Gastrointestinal Cancersmentioning

confidence: 99%

The Angiogenic Switch Molecule, Secreted FGF-Binding Protein, an Indicator of Early Stages of Pancreatic and Colorectal Adenocarcinoma

Tassi

Wellstein

2006

Seminars in Oncology

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“…Treatment of patients with metastatic renal cancer did not result in prolonged survival, although a delay in time to progression was observed (10). Yet, antiangiogenic compounds do have beneficial effects when combined with chemotherapy possibly due to normalization of the tumor vasculature (6,10,11).…”

Section: Introductionmentioning

confidence: 99%

Antiangiogenic compounds interfere with chemotherapy of brain tumors due to vessel normalization

Claes¹,

Wesseling²,

Jeuken³

et al. 2008

Molecular Cancer Therapeutics

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Glioblastomas are highly aggressive primary brain tumors. Curative treatment by surgery and radiotherapy is generally impossible due to the presence of diffusely infiltrating tumor cells. Furthermore, the blood-brain barrier (BBB) in infiltrative tumor areas is largely intact, and this hampers chemotherapy as well. The occurrence of angiogenesis in these tumors makes these tumors attractive candidates for antiangiogenic therapies.

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“…10 -12). Increased levels of VEGF expression have been found in a variety of human solid tumors, including colorectal cancer (13). A large number of clinicopathologic studies showed VEGF overexpression in 40% to 60% of colorectal cancer, a feature that is associated with increased vascular density and poor survival (14,15).…”

mentioning

confidence: 99%

Investigation of Two Dosing Schedules of Vandetanib (ZD6474), an Inhibitor of Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor Signaling, in Combination with Irinotecan in a Human Colon Cancer Xenograft Model

Troiani¹,

Serkova²,

Gustafson

et al. 2007

Clinical Cancer Research

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Purpose: This in vivo study was designed to determine the optimal doses and schedules of vandetanib, a dual epidermal growth factor receptor (EGFR)-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in combination with irinotecan in a murine xenograft model of human colon cancer. Experimental Design: HT-29 tumor-bearing nude mice were treated with two doses of vandetanib (12.5 and 25 mg/kg/d) with or without irinotecan (100 mg/kg) using either sequential or concurrent schedules for 30 days. Tumor size was measured using standard variables, whereas the antiangiogenic response was evaluated using dynamic contrast-enhanced magnetic resonance imaging. Additionally, effects on EGFR-dependent signal transduction pathways and proliferation were assessed using immunohistochemistry. These pharmacodynamic end points were then evaluated for associations with antitumor efficacy and/or to plasma/tumor concentrations of vandetanib. Results: The greatest antitumor efficacy was observed in the groups receiving the highest dose of vandetanib given continuously (concurrent schedule), alone or in combination with irinotecan. These dosing schedules resulted in significant effects on tumor vasculature, with decreased volume transfer constants, area under the curve, and permeability surface factor as well as increased gadolinium clearance after 30 days of treatment. In addition, these groups showed the greatest inhibition of EGFR signaling. Interestingly, tumor concentrations of vandetanib were increased by irinotecan in the concurrent schedule, possibly due to decreased tumor perfusion in this group. Conclusions: These data suggest that higher, sustained concentrations of vandetanib (versus intermittent), alone and in combination with irinotecan, result in optimal antitumor efficacy in this model and may have implications for the design of future clinical studies with this drug.

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Colorectal cancer and antiangiogenic therapy: What can be expected in clinical practice?

Cited by 24 publications

References 97 publications

The Angiogenic Switch Molecule, Secreted FGF-Binding Protein, an Indicator of Early Stages of Pancreatic and Colorectal Adenocarcinoma

The Angiogenic Switch Molecule, Secreted FGF-Binding Protein, an Indicator of Early Stages of Pancreatic and Colorectal Adenocarcinoma

Antiangiogenic compounds interfere with chemotherapy of brain tumors due to vessel normalization

Investigation of Two Dosing Schedules of Vandetanib (ZD6474), an Inhibitor of Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor Signaling, in Combination with Irinotecan in a Human Colon Cancer Xenograft Model

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