Chemotherapy and Angiogenesis in Advanced Cancer: Vascular Endothelial Growth Factor (VEGF) Decline as Predictor of Disease Control during Taxol Therapy in Metastatic Breast Cancer

Abstract

Angiogenesis is essential for tumor growth. Since vascular endothelial growth factor (VEGF) represents the main angiogenic factor, the control of VEGF secretion could constitute the most important mechanism to achieve the inhibition of angiogenesis-related processes. High blood concentrations have been proven to correlate with poor prognosis in advanced cancer. In experimental conditions, chemotherapeutic agents such as taxol appeared to inhibit VEGF-induced angiogenesis, while at present there are no data about the influence of chemotherapy on VEGF secretion in cancer patients. This preliminary study was performed to evaluate the effect of taxol therapy on VEGF secretion in advanced cancer patients in relation to the clinical response. The study included 14 patients with metastatic breast cancer who were treated with taxol monochemotherapy (175 mg/m2 i.v. every 21 days for three cycles). Serum levels of VEGF were measured by ELISA in blood samples collected before therapy and at 21-day intervals. The clinical response consisted of partial response (PR) in three and stable disease (SD) in six patients, whereas the other five patients had progressive disease (PD). Abnormally high pre-treatment levels of VEGF were seen in 8/14 patients. VEGF mean values significantly decreased during taxol therapy in patients with PR or SD, whereas no decline was observed in patients with PD. Moreover, the percent of normalization or decline greater than 50% in VEGF levels was significantly higher in patients with PR or SD than in those with PD (5/9 vs. 0/5). This preliminary study would suggest that the efficacy of taxol therapy in metastatic breast cancer - at least in terms of disease stabilization - may be associated with a decrease in VEGF blood levels followed by potential inhibition of cancer-related neovascularization.

Circulating levels of angiogenic cytokines in advanced breast cancer patients with system chemotherapy and their potential value in monitoring disease course

“…Currently, the prediction of survival for patients with advanced breast cancer is often inaccurate. The accumulating evidence indicated that the pretreatment serum VEGF level could have the predictive potential (Shivakumar et al 2009;Karayiannakis et al 2003;Dudek and Mahaseth 2005;Lissoni et al 2000). This study not only confirmed the association of pretreatment serum VEGF level with patient survival (Fig.…”

“…Some studies have confirmed the importance of socalled metronomic chemotherapy in preclinical models (Colleoni et al 2002). However, the conclusions on the impact of system chemotherapy on secretion of angiogenic factors from tumor and/or other cells are discordant (Tas et al 2008;Lissoni et al 2000). This work observed the changes of serum VEGF and ES levels during system chemotherapy for patients with advanced breast cancer and assessed their value in predictive and prognostic judgment.…”

Class III β-Tubulin Isotype Predicts Response in Advanced Breast Cancer Patients Randomly Treated Either with Single-Agent Doxorubicin or Docetaxel

“…However, other studies seem to suggest no interactions between HER2 status and taxane therapy (11, 12). Similar conflicting results were observed for other biomarkers such as the apoptotic index (9), p53 (12, 13), proliferation markers (14), and angiogenic-related markers (15,16). Thus, markers that help predict whether a patient might benefit more from a taxane-based than from an anthracycline-based regimen are clearly needed.…”

Targeting Microtubules to Inhibit Angiogenesis and Disrupt Tumour Vasculature:Implications for Cancer Treatment

“…The discovery of reliable markers may indeed allow the optimization of MTA dosing and the combination with other anti-angiogenic agents. Potential approaches to evaluate the efficacy of anti-vascular therapies are tumour blood flow assessed by new imaging techniques, serum or urine pro-and anti-angiogenic cytokine profiles, soluble vascular cell adhesion molecule (sVCAM) and soluble intercellular adhesion molecule (sICAM) [162,214,241,258]. Many of these activators or inhibitors of angiogenesis are soluble proteins, whose circulating levels could reflect the overall angiogenic activity of the tumour.…”