Very recently, an anti-VEGF monoclonal antibody (bevacizumab; Avastin) has been approved by the Food and Drug Administration as a first-line treatment for metastatic colorectal cancer in combination with chemotherapy.
Bevacizumab (Avastin(TM)), a monoclonal antibody against VEGF, was efficient in two randomized clinical trials investigating the treatment of metastatic colorectal cancer.
To investigate whether mRNA expression levels of cyclin D1 (CCND1), cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), interleukin 8 (IL-8), and vascular endothelial growth factor (VEGF), all members of the EGFR signaling pathway, are associated with clinical outcome in patients with EGFR-expressing metastatic colorectal cancer (CRC) treated with cetuximab.
A recent phase III trial showed that the addition of bevacizumab, a monoclonal antibody to vascular endothelial growth factor-A, to first-line irinotecan, 5-fluorouracil, and leucovorin (IFL) prolonged median survival in patients with metastatic colorectal cancer.
Impact of vascular endothelial growth factor-A expression, thrombospondin-2 expression, and microvessel density on the treatment effect of bevacizumab in metastatic colorectal cancer.
Avastin (bevacizumab), a vascular endothelial growth factor (VEGF) specific monoclonal antibody in combination with chemotherapy is offering hope to patients with metastatic colorectal cancer.
In an attempt to elucidate the relationship between biomarkers of tumor hypoxia, glycolysis and angiogenesis, we tested the hypothesis that intratumoral gene expression of the hypoxia response (hypoxia inducible factor [HIF1 alpha and 2 alpha]), glycolysis (lactate dehydrogenase A [LDHA]), glucose metabolism (glucose transporter-1 [Glut-1]) and genes involved in angiogenesis (i.e., VEGFA, VEGFR1-3, and neuropilin [NRP]1) are upregulated in metastatic colorectal cancer (mCRC) patients with high serum lactate dehydrogenase (LDH).
This article reviews the results of prospective randomized clinical trials of anti-VEGF and anti-EGFR antibodies in mCRC, either as monotherapy, combined with chemotherapy, or combined with each other.
Our results support a genetic interaction between the TYMS enhancer region and VEGF +405G>C polymorphisms as a predictor of the efficacy of CAPOX-B in mCRC patients.
Predictive value of VEGF gene polymorphisms for metastatic colorectal cancer patients receiving first-line treatment including fluorouracil, irinotecan, and bevacizumab.
Vascular endothelial growth factor (VEGF) is a key player in tumor angiogenesis and the target for the MoAb bevacizumab, which is currently licensed for use in mCRC.
Plasma levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble VEGF receptor 2 (sVEGFR-2) and thrombospondin-1 (TSP-1) were assessed by ELISA assay at different time points in a cohort of 25 patients enroled in a phase II trial of GONO-FOLFOXIRI plus BV as first-line treatment of mCRC.
These data suggest a possible role for VEGF-1498 C/T variants in predicting the efficacy of bevacizumab in the up-front treatment of metastatic colorectal cancer patients.
In this study, we identified common germline variants in VEGF-dependent and -independent angiogenesis genes predicting clinical outcome and tumor response in patients with mCRC receiving first-line bevacizumab and oxaliplatin-based chemotherapy.
Our results support the potential predictive ability of VEGF genotypes in patients with metastatic colorectal cancer receiving irinotecan-based chemotherapy plus bevacizumab, in terms of RR and OS.
The predictive value of single nucleotide polymorphisms in the VEGF system to the efficacy of first-line treatment with bevacizumab plus chemotherapy in patients with metastatic colorectal cancer: results from the Nordic ACT trial.
We hypothesized that gene expression levels and germline variations in CD133 will predict clinical outcome in patients with metastatic colorectal cancer (mCRC), treated in first-line setting with 5-fluorouracil, oxaliplatin and bevacizumab (BV), and we investigated whether there is a correlation with gene expression levels of CD133, vascular endothelial growth factor (VEGF) and its receptors.
Therefore, a priori molecular identification of patients that could benefit from anti-EGFR or anti-VEGF monoclonal antibodies (i.e. the currently approved targeted therapies for metastatic colorectal cancer) is of critical importance.
This study demonstrated a significant relation between a lower incidence of grade 2 or higher bevacizumab-related hypertension and the VEGF-2578 C/C genotype for the entire treatment period in Japanese patients with metastatic colorectal cancer.
Maintenance of VEGF inhibition with bevacizumab plus standard second-line chemotherapy beyond disease progression has clinical benefits in patients with metastatic colorectal cancer.
The anti-VEGF monoclonal antibody bevacizumab was approved in 2004 as a first-line treatment for metastatic colorectal cancer (CRC) in combination with chemotherapy and provided proof of principle for antiangiogenic therapy.
Targeting angiogenic factors from the VEGF family has become an effective strategy to inhibit tumor growth and so far the most successful results are seen in metastatic colorectal cancer (CRC), renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLL).