Angiogenesis inhibitors in cancer therapy: mechanistic perspective on classification and treatment rationales

Abstract

Angiogenesis, a process of new blood vessel formation, is a prerequisite for tumour growth to supply the proliferating tumour with oxygen and nutrients. The angiogenic process may contribute to tumour progression, invasion and metastasis, and is generally accepted as an indicator of tumour prognosis. Therefore, targeting tumour angiogenesis has become of high clinical relevance. The current review aimed to highlight mechanistic details of anti-angiogenic therapies and how they relate to classification and treatment rationales. Angiogenesis inhibitors are classified into either direct inhibitors that target endothelial cells in the growing vasculature or indirect inhibitors that prevent the expression or block the activity of angiogenesis inducers. The latter class extends to include targeted therapy against oncogenes, conventional chemotherapeutic agents and drugs targeting other cells of the tumour micro-environment. Angiogenesis inhibitors may be used as either monotherapy or in combination with other anticancer drugs. In this context, many preclinical and clinical studies revealed higher therapeutic effectiveness of the combined treatments compared with individual treatments. The proper understanding of synergistic treatment modalities of angiogenesis inhibitors as well as their wide range of cellular targets could provide effective tools for future therapies of many types of cancer.

Qualification of a Noninvasive Magnetic Resonance Imaging Biomarker to Assess Tumor Oxygenation

“…We were able to observe a positive correlation between the R 1 values of lipids and absolute pO 2 When all the data were pooled, a significant correlation was established between the R 1 values of lipids and the pO 2 values (P ¼ 0.0275, r ¼ 0.3726; Fig. 4).…”

“…A change in the R 1 of lipids is related to a change in the tumor pO 2 While pooling data from 20 different tumors (10 of each tumor model), we can observe a significant correlation between the DR 1 of lipids (MOBILE) and the DpO 2 in the same tumors (P ¼ 0.0059, r ¼ 0.5097; Fig. 2A), whereas similar analysis using the global R 1 does not give a significant correlation (Fig.…”

The ketogenic diet for the treatment of malignant glioma

“…In addition, a separate study showed that 9 out of 11 animals maintained on the UKD and treated with radiation had complete and sustained remission of their implanted tumors, even after being switched back to a standard rodent diet ( 58 ). Another recent study Tumors not only stimulate rapid angiogenesis, but these blood vessels often develop immaturely and become very leaky ( 52 ). This can lead to an increased infl ux of infl ammatory cells and signaling that can actually perpetuate tumor growth and damage surrounding normal tissue.…”

A Novel Image Analysis Methodology for the Evaluation of Angiogenesis in Matrigel Assays and Screening of Angiogenesis-Modulating Compounds

“…One of the challenges researchers initially faced was the selection of scientifically and technically efficient methods for assessing the endothelial response to candidate angiogenesis inhibitors [5]. Ideally, an assay should be valid, methodologically straightforward, easily quantifiable, cost-effective and able to provide an environment simulating the natural angiogenic process under study.…”