Are tumours angiogenesis‐dependent?

Abstract

The final proof of principle that cancer patients can be effectively treated with angiogenesis inhibitors is eagerly awaited. Various preclinical in vivo experiments have proven that most tumours need new vessel formation in order to grow and to form metastases. First of all, tumours do not grow in avascular corneas until new blood vessels reach the implant. Secondly, the introduction of only one angiogenic gene can cause a switch from tumour dormancy to progressive tumour growth. Thirdly, tumour growth can be inhibited and sometimes tumour regression can be obtained just by attacking the vascular compartment with specific angiogenesis inhibitors. These three examples of preclinical experiments and many others have led to the conclusion that, in general, tumours are angiogenesis-dependent. Supported by disappointing clinical results, the angiogenesis dependency of tumours has been questioned, mainly because of the immaturity and the presumed lack of a functional blood supply (oxygen delivery and discarding of waste products) from a newly formed tumour vasculature. However, human tumours are highly heterogeneous in vascular architecture, differentiation, and functional blood supply. Vascular immaturity is a natural consequence of a genetically based unlimited expansion of tumour cells, compared to the well-regulated growth of different organs during embryonic development, for example. Unlimited tumour expansion and therefore the continuous stimulation of vessel outgrowth prevent endothelial cells from generating a mature vasculature, but instead continuously stimulate them to expand the vascular compartment of the growing tumour. In this review, the translation of angiogenesis inhibitors as a treatment for cancer from preclinical experiments to the clinic is evaluated. The preclinical evidence that tumours are angiogenesis-dependent is summarized and explanations are put forward for why the clinical results so far are not as exciting as was expected from preclinical studies. Reviewing the translation, one may conclude that human tumours are heterogeneous in their vascular architecture and function and that tumour-induced angiogenesis in humans is a more complex (multifactorially regulated) process compared with angiogenesis in preclinical cancer models.

Novel antibodies as anticancer agents

“…These unusual features provide some molecular and structural basis for selective inhibition or even destruction of tumor vessels by angiogenesis inhibitors (Cao, 2004). By attacking the vascular compartment with specific angiogenesis inhibitors, tumor growth can be inhibited and sometimes tumor regression can be obtained (Verheul et al, 2004). However, several clinical trials have shown mild results, and resistance to the treatment has also been observed.…”

Diagnostic Accuracy of Dynamic Contrast-Enhanced MR Imaging Using a Phase-Derived Vascular Input Function in the Preoperative Grading of Gliomas

“…Physiologic imaging such as perfusion MR imaging has been used recently to evaluate angiogenesis, which is important for both the growth and metastasis of malignant tumors. 2 The 2 most common MR perfusion techniques used in clinical practice are dynamic susceptibility-weighted contrast-enhanced imaging and DCE imaging. 3 Following an intravenous injection of a Gd-based contrast agent, dynamic susceptibilityweighted contrast-enhanced imaging measures the change in R 2 * during the first pass of the bolus, while DCE imaging measures the changes in R 1 during both the first pass and washout phases.…”

Tumor Vascular Interaction in Melanomas and Neurogenesis: A Review

“…Angiogenesis is the sprouting of blood vessels from preexisting ones where endothelial buds grow out towards the tumor margins [32][33][34][35][36]. Reciprocal paracrine interactions between astrocytes, endothelial cells and ependymal cells have been demonstrated in recent studies.…”