Modulation of Tumor Vasculature Network: Key Strategies

Abstract

Tumor cells, owing to their relentless division, require increased nutrient supply. This is made possible by angiogenesis, that is, the formation of new blood vessels increases the blood flow toward tumor cells, thereby promoting the supply of oxygen and vital nutrients required for the proliferation of tumor cells. Decreasing the blood flow to the tumor cells can effectively halt tumor progression and possibly cure cancer. However, practically, the mechanism is not as straightforward as it seems. In this review, the role of angiogenesis is focused on in the development of tumors and cancer metastasis and the potential of tumor vascular normalization for the reduction of angiogenesis, which results in the suppression of tumor cells. An insight into various strategies, including pharmacological inhibition of angiogenesis, genetic models, and nanoparticle‐based novel treatment strategies for vascular normalization, is provided. In addition, the effect of vessel normalization and tumor microenvironment modulation on the delivery of nanoparticle‐based drugs to the target tumor cells is discussed. The critical role of monitoring vascular normalization is also highlighted, without which selecting the most efficient strategy for tumor vascular normalization is possible. Therefore, efficiently combating cancer and its devastating effects remains an unsolved puzzle.

Normalizing Tumor Blood Vessels to Improve Chemotherapy and Inhibit Breast Cancer Metastasis by Multifunctional Nanoparticles

“…The abnormality of the tumor vascular structure can increase the leakiness. 20,40 Compared with the saline group, in the group containing only DOX, the leakage of FITC-dextran in the tumors was obvious. The result indicated that DOX destroyed tumor blood vessels and increased the possibility of tumor metastasis.…”

Nanomedicine Remodels Tumor Microenvironment for Solid Tumor Immunotherapy

“…Currently, several approaches can be used to achieve tumor vascular normalization, including employing anti-VEGF drugs to block the expressions of angiogenic factors and the antibody MEDI3617 to inhibit angiopoietin-2 (Ang-2) . Numerous nanoparticles targeting the VEGF pathway have been established for tumor vascular normalization . Nevertheless, studies concentrating on enhancing tumor immunotherapy via intratumoral angiogenesis remain relatively rare.…”

Vascular Endothelial Growth Factor-D (VEGF-D): An Angiogenesis Bypass in Malignant Tumors

“…The newly formed vessels are then covered by tumor-recruited pericytes, which provide support to the vessels from outside (maturation step) (Figure 3) [95]. Unlike normal blood vessels, blood vessels in tumors are more permeable and tortuous, which is attributed to the altered endothelial cells (ECs) referred to as Tumor Endothelial Cells (TECs) [96,97]. Furthermore, besides the autocrine production of proangiogenic factors by tumor cells, tumor cells can prime immune cells to produce more angiogenic factors, which results in a loss of balance between the pro and antiangiogenic factors, rendering the tumor vasculature unruly and poorly developed [98].…”