Cancer prevention by targeting angiogenesis

Abstract

Healthy individuals can harbour microscopic tumours and dysplastic foci in different organs in an undetectable and asymptomatic state for many years. These lesions do not progress in the absence of angiogenesis or inflammation. Targeting both processes before clinical manifestation can prevent tumour growth and progression. Angioprevention is a chemoprevention approach that interrupts the formation of new blood vessels when tumour cell foci are in an indolent state. Many efficacious chemopreventive drugs function by preventing angiogenesis in the tumour microenvironment. Blocking the vascularization of incipient tumours should maintain a dormancy state such that neoplasia or cancer exist without disease. The current limitations of antiangiogenic cancer therapy may well be related to the use of antiangiogenic agents too late in the disease course. In this Review, we suggest mechanisms and strategies for using antiangiogenesis agents in a safe, preventive clinical angioprevention setting, proposing different levels of clinical angioprevention according to risk, and indicate potential drugs to be employed at these levels. Finally, angioprevention may go well beyond cancer in the prevention of a range of chronic disorders where angiogenesis is crucial, including different forms of inflammatory or autoimmune diseases, ocular disorders, and neurodegeneration.

Therapeutic Targeting of Angiogenesis with a Recombinant CTT Peptide–Endostatin Mimic–Kringle 5 Protein

“…The crux of clinical validation of antiangiogenic therapy lies in the fact that cancer is still usually treated at advanced, often metastatic, disease stages (45). In the setting of heavy disease burden, most patients treated with antiangiogenic agents eventually experience disease progression due to evolution of biologic escape mechanisms by tumors (46,47). What has emerged from our work is that the utility of tumor angiogenesis inhibition in the clinic should be tumor context dependent.…”

Licochalcone E Present in Licorice Suppresses Lung Metastasis in the 4T1 Mammary Orthotopic Cancer Model

“…The uncontrolled growth of solid tumor and metastasis are directly related to tumor angiogenesis by delivering oxygen and nutrients for the survival of rapidly proliferating tumor cells in addition to providing routes for the spread of tumor cells. Therefore, blocking the vascularization of incipient tumors can be a very effective strategy to inhibit tumor promotion (4). LicE treatment reduced CD31þ cells as well as the expression of VEGF-A and its mitogenic receptor VEGF-R2 in tumor tissues (Fig.…”

“…These tumors do not progress in the absence of inflammation or angiogenesis, which are 2 host-dependent and interdependent hallmarks of cancer [reviewed in (4)]. Chronic inflammation promotes angiogenesis (5) and inflammatory reactions play crucial functions at multiple phases of cancer development including initiation, promotion, malignant conversion, invasion, and metastasis [reviewed in (6)].…”

Performance Optimisations for a Numerical Solution to a 3D Model of Tumour-Induced Angiogenesis on a Parallel Programming Platform

“…A key mechanism of antiangiogenic therapy is to interfere with the process of blood vessel growth and literally starve the tumour of its blood supply. Indeed, a new class of cancer treatments that block angiogenesis have recently been approved and available to treat cancers of the colon, kidney, lung, breast, liver, brain, ovaries and thyroid [3][4][5][6][7]. Angiogenesis is without doubt a complex biological phenomena and one that at a cellular level is dynamic, spatially heterogeneous, frequently non-linear, and spans many orders of magnitude, both spatially and temporally.…”