Cancer Cells: Starving them Out


Research published in Nature earlier this month has demonstrated the requirement of fatty acids for the formation of new blood vessels; a crucial process in the survival of cancers. Scientists from Flanders Interuniversity Institute for Biotechnology have succeeded in inhibiting this pathway, providing the basis for a potential new treatment that effectively starves cancer cells.

There are a number of ways in which cancerous cells must adapt to survive in our bodies, an environment where the balance between cell division and death is normally tightly regulated. Once a cancer has reached 1 to 2mm across, it must become more vascularised – form more blood vessels to give it a constant supply of oxygen and glucose, and remove waste – to sustain uncontrolled division, a hallmark of cancer cells. Moreover, the ability of cancer to spread to other organs, propagating its lethal effects and complicating treatment, depends on the ability of tumour cells to enter the blood. The cells which make up blood vessels must divide in the process of angiogenesis to allow ‘vessel sprouting’, causing them to extend into a tumour. As such, there have been many attempts to counteract this process by blocking the function of angiogenic factors. These attempts have hitherto been inefficient and easily bypassed by cancer cells in the production of a distinct angiogenic factor.

We still have a long road … before bench-side theory becomes bedside practice

CPT is an enzyme responsible for shuttling fatty acids into mitochondria, the power stations of the cell. Mitochondria use fatty acid oxidation to produce energy for the synthesis of DNA and proteins, all of which are crucial to cell survival and division. Silencing CPT1a in mice reduced cell division in blood cells, indicating a defect in angiogenesis. They found that products of fatty acid breakdown, detected by radioactive labels, were used to synthesise DNA which was impaired when CPT1a was silenced. Moreover, angiogenesis was rescued when precursors of nucleotides, the building blocks of DNA, called nucleosides were added to the endothelial cells. Therefore, by impairing DNA synthesis, CPT1a silencing has the potential to inhibit endothelial division and, consequently, angiogenesis. Moreover, pathological angiogenesis was inhibited when a blocker of CPT1a called etoxomir was tested in mouse models. The use of fatty acids by endothelial cells in the production of DNA is distinct to that of most other cells which rely mainly on the availability of sugar and amino acids, as was previously thought to be the case with endothelial cells. Identifying such pathways unique to a cell type is crucial for selective targeting, making fatty acid metabolism an excellent candidate for a novel anti-angiogenic.

These insights could form the basis of a novel strategy for blocking pathological angiogenesis by lowering fatty acid oxidation to starve endothelial cells, therefore cancer cells. The prevention of angiogenesis would also prevent the spread of cancer through the blood, a crucial stage in improving survival rates among cancer patients. Dr. Maria-Fendt states that their new-found insight is “ground breaking and has the potential to have a major impact on the treatment of disease with vascular involvement such as cancer”. Indeed, this research could have implications in other diseases; uncontrolled angiogenesis can cause blindness by the destruction of the retina due to leakage of blood, underlying the pathology of many diseases such as age-related macular degeneration. However, as Dr. Carmeliet warns, “We still have a long road with many years of research” before bench-side theory becomes bedside practice.


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