How to starve the cancer cells? I hope this article provides some insights on this topic.
The Mechanism of Tumor Angiogenesis
Cancer cells require fuels such as nutrients and oxygen to survive and grow. Therefore, they must have access to the blood circulation system. If there is a lack of blood supply, tumors remain dormant. The term “angiogenesis” refers to the growth of new blood vessels required for tumor growth. Cellular angiogenesis is one of the most important hallmarks of cancer and plays a vital role in cancer development. (Al-Ostoot et al., 2021; Lugano et al., 2020)
With a multi-step mechanism of angiogenesis, cells, and extracellular components interact actively and extensively. In growing cancers, the concentration of anti-angiogenic factors is reduced, making endothelial cells active. This is because the released proteins (VEGF, EGF, FGF, IL-8, and TNF) can initiate the growth and migration of endothelial cells, leading to cell mutation and a highly vascularized tumor state. Important triggers of angiogenic signaling include oncogene-mediated protein expression and different cellular stressors such as hypoxia, nutrient deficiencies, low pH, and ROS. (Al-Ostoot et al., 2021)
The understanding of the mechanism of angiogenesis ultimately led to the design and development of anti-angiogenic therapy for clinical application as an essential strategy for cancer treatment.
Pharmaceutical angiogenesis inhibitors
Anti-angiogenic drugs were developed to suppress new blood vessel formation and interfere with cancer development. These inhibitors are monoclonal antibody molecules that recognize and bind the VEGF protein, inhibiting and reducing its activity. This process prevents the VEGF protein from activating its receptors on the endothelial cell surface.
Angiogenesis inhibitors do not function to kill cancerous cells. But instead, they target the signals, aiming to cut the blood supply the tumor needs for survival. Studies have shown that the efficacy of the current anti-angiogenic therapies is limited due to intrinsic and acquired resistance. However, they are more effective when combined with other treatments, such as chemotherapy, to prevent the formation of new blood vessels and reduce tumor mass. (Al-Ostoot et al., 2021) (Lugano et al., 2020)
Future development will require a deeper understanding of blood vessel mechanisms involved in response to cancer therapy to more effectively control the angiogenic response in tumors. Maybe the focus could be on finding new ways to target the tumor vessels differently from angiogenesis inhibition. (Lugano et al., 2020)
Currently, the types of pharmaceutical angiogenesis inhibitors designed to block blood vessel growth include: (Drugs That Block Cancer Blood Vessel Growth (Anti Angiogenics) | Targeted Cancer Drugs | Cancer Research UK, n.d.)
To block blood vessel growth factors: An example is bevacizumab (Avastin). Bevacizumab is also a monoclonal antibody as a treatment for several different types of cancer. Other examples include aflibercept and ramucirumab.
To block signaling within the cell - cancer growth blockers or tyrosine kinase inhibitors (TKIs): Examples include sunitinib, sorafenib, axitinib, regorafenib, and cabozantinib.
To affect signals between cells: Examples include thalidomide and lenalidomide (Revlimid).
Natural Angiogenesis Inhibitors
Many natural health products (herbs and functional foods) possess anti-angiogenic activity and other anticancer activities. They can be utilized as therapeutic options in treating cancer. These natural agents present anti-angiogenic effects through multiple interrelated and interactive processes, including effects on enzyme activities, gene expression, and signaling processing. Given these various anti-cancer effects, they should be considered and applied as adjunct therapies in combination with chemotherapy and radiation therapies. In this process, they have the potential to enhance the efficacy of conventional treatments for their ability to function as adaptogens or modifiers of biological response. (Sagar et al., 2006)
Here is a list of natural agents with anti-angiogenic activity and anti-cancer effects:
Capsaicin (cayenne pepper)
Artemisia annua (Chinese wormwood)
Viscum album (European mistletoe)
Curcuma longa (curcumin)
Scutellaria baicalensis (Chinese skullcap)
Resveratrol
Turmeric
Proanthocyanidin (grape seed extract)
Magnolia officinalis (Chinese magnolia tree)
Camellia sinensis (green tea)
Ginkgo biloba
Quercetin
Poria cocos
Zingiber officinalis (ginger)
Panax ginseng
Rabdosia rubescens hora (Rabdosia)
Chinese destagnation herbs
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References:
Al-Ostoot, F. H., Salah, S., Khamees, H. A., & Khanum, S. A. (2021). Tumor angiogenesis: Current challenges and therapeutic opportunities. Cancer Treatment and Research Communications, 28, 100422. https://doi.org/10.1016/J.CTARC.2021.100422
Drugs that block cancer blood vessel growth (anti angiogenics) | Targeted cancer drugs | Cancer Research UK. (n.d.). Retrieved September 16, 2022, from https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/targeted-cancer-drugs/types/anti-angiogenics
Lugano, R., Ramachandran, M., & Dimberg, A. (2020). Tumor angiogenesis: causes, consequences, challenges and opportunities. Cellular and Molecular Life Sciences, 77(9), 1745–1770. https://doi.org/10.1007/S00018-019-03351-7/FIGURES/3
Sagar, S. M., Yance, D., & Wong, R. K. (2006). Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer—Part 1. Current Oncology, 13(1), 14. /pmc/articles/PMC1891166/