Cancer cells can when the blood supply is low use lipid molecules as fuel instead of blood glucose, according to a study using animal tumor models. The mechanism may help explain why tumors often develop resistance to cancer drugs that inhibit the formation of blood vessels.
But before we dive into the research details, let us remind ourselves of what lipids are and their position in the body.
The most important of all lipids includes
- fats and oils,
and we shall be summarising them one after the other
A fat molecule consists of two kinds of parts: a glycerol backbone and three fatty acid tails. Glycerol is a small organic molecule with three hydroxyl (OH) groups, while a fatty acid consists of a long hydrocarbon chain attached to a carboxyl group. A typical fatty acid contains 12–18 carbons, though some may have as few as 4 or as many as 36.
Fatty acids rarely occur as free molecules in nature but are usually found as components of many complex lipid molecules such as fats (energy-storage compounds) and phospholipids (the primary lipid components of cellular membranes). This section describes the structure and physical and chemical properties of fatty acids.
Waxes are another biologically important category of lipids. Wax covers the feathers of some aquatic birds and the leaf surfaces of some plants, where its hydrophobic (water-repelling) properties prevent water from sticking to, or soaking into, the surface.
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What keeps the watery goo (cytosol) inside of your cells from spilling out? Cells are surrounded by a structure called the plasma membrane, which serves as a barrier between the inside of the cell and its surroundings.
Specialized lipids called phospholipids are major components of the plasma membrane. Like fats, they are typically composed of fatty acid chains attached to a backbone of glycerol.
Steroids are another class of lipid molecules, identifiable by their structure of four fused rings. Although they do not resemble the other lipids structurally, steroids are included in lipid category because they are also hydrophobic and insoluble in water.
Now back to where we were
Tumour growth and spread rely on angiogenesis, a process of growing new blood vessels that supply the cancer cells with nutrients and hormones, including glucose (sugar).
Treatment with antiangiogenic drugs reduces the number of blood vessels in the tumour as well as the blood glucose supply.
Many such drugs have been developed and are now used in human patients for treating various cancer types.
However, the clinical benefits of antiangiogenic drugs in cancer patients are generally low and the cancers treated often develop a resistance to drugs, especially cancer types that grow close to fat tissues such as breast cancer, pancreatic cancer, liver cancer and prostate cancers.
In collaboration with Japanese and Chinese scientists, a research group at Karolinska Institutet in Sweden has discovered a new mechanism by which cancers can evade antiangiogenic treatment and become resistant.
The reduction of tumour blood vessels results in low oxygenation in tumour tissues a process called hypoxia. In the current study, the researchers show that hypoxia acts as a trigger to tell fat cells surrounding or within tumour tissues to break down the stored excessive lipid energy molecules.
These lipid energy molecules can when the blood supply is low be used for cancer tissue expansion.
“Based on this mechanism, we propose that a combination therapy consisting of antiangiogenic drugs and drugs blocking lipid energy pathways would be more effective for treating cancers. In animal tumour models, we have validated this very important concept, showing that combination therapy is superior to monotherapy,”
says Yihai Cao, Professor at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet, who led the study.
Professor Cao’s group now plans to work with drug companies and clinical oncologists to explore whether such a new combination therapy would improve the quality of life and lifespan in human cancer patients.