By Rose Faure - Medicine Student @ Trinity College, Oxford
Angiogenesis is the process by which new blood vessels are formed from pre-existing vessels. This process is vital for the continued delivery of oxygen and nutrients; however it also plays a role in pathology that could be exploited in order to design new cancer treatments.
Normal angiogenesis can normally be observed in the embryo, or in tissues that are healing or growing and thus need to establish an efficient blood supply. The process relies upon chemical signalling within the body to induce endothelial cells to migrate, grow, and differentiate to eventually form new vasculature. Among many other signals, vascular endothelial growth factor (VEGF) plays perhaps the most important role in bringing about this series of events.
Whilst angiogenesis is seen in normal physiological states, tumour-induced angiogenesis is seen in pathological states and results in abnormal changes to the vascular tree. This rapid angiogenesis is more commonly associated with malignant (or cancerous) tumours, however it has also been observed at a slower rate in benign tumours. These tumours, which can be thought of as abnormal masses of tissue, release signalling molecules that result in activation of specific genes and in turn growth of new blood vessels. Angiogenesis is specifically important in the growth of cancer, as without a sufficient blood supply the tumours would be unable to grow much larger than a few millimetres in size. Without reaching a large enough size, cancer cells would be unable to invade neighbouring tissues or spread through the body via metastases. In fact, angiogenesis is so critical to cancer growth that a 1970s experiment proved that the formation of cancer is dependent on angiogenesis. Clearly, angiogenesis provides a valuable target for the development of new cancer treatments and therapies.
Perhaps the most obvious target is the VEGF protein growth factor that is required by cancer cells to recruit nearby cells and stimulate angiogenesis. In order to target this clinically, angiogenic inhibitors are being used – these are drugs which act to block the growth of blood vessels which would be needed to support the tumour. Whilst they do not block tumours from growing, they do prevent them from establishing the necessary vasculature to grow and metastasise. Some angiogenic inhibitors are monoclonal antibodies that are specific to VEGF; this allows them to bind to VEGF and prevent the growth factor from binding to receptors on the surface of endothelial cells. Alternatively, angiogenic inhibitors may be immunomodulatory drugs, meaning that they alter the manner in which the immune system functions whilst also being able to modulate angiogenesis.
Currently, there are a number of these drugs that have been approved for clinical use in cancer treatment – these have been seen to be most effective in the treatment of cancers such as those of kidney, colon, rectum, and stomach. These treatments are often used in conjunction with other therapies such as chemotherapy. Nonetheless, the treatment does not seem to be effective in all cancers, and often only has a minor impact on overall survival rates, so there is certainly still work to be done in the field before angiogenic inhibitors become major players in the treatment of cancer.
Further reading:
https://www.mskcc.org/news/what-angiogenesis
https://journals.physiology.org/doi/full/10.1152/ajpcell.00389.2001
https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/angiogenesis-inhibitors-fact-sheet