Blocking fatty acid uptake: a new approach to treating prostate cancer

[Wendy_Winnall]

A new Australian study has uncovered a weakness in prostate cancer cells. The researchers studied the energy needs of prostate cancer cells grown in the laboratory and in mice. Their results indicate that blocking fatty acid uptake may slow the progression of prostate cancer. This week’s research blog describes the latest findings, discusses fatty acids, and whether we need to avoid them.

Obesity and prostate cancer

Obesity is a major problem in Australia. Almost two thirds of Australians are considered overweight and over a quarter are considered obese (AIHW statistics, 2018). People who are obese have a higher chance of suffering poor health. There is evidence that obesity is associated with aggressive prostate cancer. Men who are obese are more likely to get aggressive prostate cancer. They are also more likely to die from prostate cancer than those who are not obese.

That obesity brings a risk of aggressive prostate cancer does not mean that obesity is the only cause of this disease. Men who are not obese also get prostate cancer. It’s believed that many different risk factors combine together to cause the damage to DNA that causes prostate cancer. Many of these risk factors are things that we can’t do anything about.

Far from blaming men for their disease, the Melbourne researchers behind this new study have gained a new understanding of what is different about the way prostate cancer cells use energy sources. The results of their study have uncovered a weakness in the prostate cancer cells that could be exploited by drugs. Hopefully a new type of treatment will result from this knowledge.

Prostate cancer cell metabolism

Humans have a metabolism - our food is broken down, energy is generated and waste products are formed. In a similar way, individual cells have their own metabolism. Metabolism, in this case, refers to the chemical reactions inside of the cell that make energy and the cell’s infrastructure. Cells take up carbohydrates, proteins and fats, which are turned into energy, cellular building blocks and waste products.

The metabolism of cancer cells appears to be different to normal cells. This is not surprising, as tumours often grow very quickly compared to normal tissues. Certain types of PET scans can be used to detect tumours because they use a lot of glucose to grow.

But not all cancers are the same. Prostate cancers do not show up well on the PET scans that look for fast uptake of glucose. It turns out that prostate cancer cells don’t use a large amount of glucose, like most other cancer cells.

Two recent discoveries set the scene for this new Australian project: 1) prostate cancer cells grown in the laboratory mainly use fatty acids as an energy source, and 2) a diet high in saturated fats for men with localised prostate cancer increases their risk of dying. This led researchers Prof Matthew Watt and A/Prof Renea Taylor to predict that blocking fatty acid use as energy could slow the progression of prostate cancer.

What are fatty acids?

Fatty acids are molecules found in many fatty foods. There are many different types of fatty acids, including the unsaturated, saturated and trans fats that we commonly eat. Although some fatty acids are part of a healthy diet, many people eat too many, or the wrong kinds. Many of the fatty acids that we eat are not considered healthy, such as saturated and trans fats.

The Australian study did not address fatty acids in the diets of men with prostate cancer. Rather they looked at what was going on inside the body. There are good reasons for this. Cells take up fatty acids from difference origins. One is from fatty acids eaten in our diets. Another is from fatty acids produced in our bodies by a process called de novo lipogenesis. This refers to the conversion of carbohydrates into fatty acids as storage. When a lot of carbohydrates are eaten, the excess ones are converted into fatty acids, to be stored in the body. This mostly occurs in the liver and in fat cells. When someone hasn’t eaten for a while, fatty acids are released from the fat storage and used as energy. So cancer cells can get their energy from fatty acids that were made in the body, rather than eaten by the patient.

New Australian study

The Australian researchers are based in Melbourne and work at the University of Melbourne, Monash University and other top research institutes around the country. Their successful project was funded by PCFA through a Movember New Concept Award to Prof Matthew Watt. Their findings were published in the highly-ranked journal Science Translational Medicine.

The Australian team made a number of discoveries about how prostate cancer cells use fatty acids as an energy source. They showed that more fatty acids are taken into prostate cancer cells than normal cells. These experiments were done on human prostate cancer cells grown in the laboratory. They then studied a fatty acid transporter molecule called CD36. This protein is located on the cell surface and helps the cell to take in fatty acids. The researchers wondered if CD36 played a crucial role in tumour growth. Using mouse experiments, they showed that:

- Removing CD36 from mice meant that less fatty acids were taken in to prostate cancer cells growing in the mice,

- Mice with no CD36 had slower progression of prostate tumours to an aggressive form,

- An inhibitor of CD36 could reduce the severity of cancer in mice with transplants of human cancer cells.

These results indicate that the fatty acid transporter molecule called CD36 could be a new target for treating prostate cancer.

More exciting results came from testing a dual-targeting experiment. The researchers used two different drugs to slow prostate cancer growth. One inhibited fatty acid uptake by targeting of CD36. The other inhibited the conversion of carbohydrates into fatty acids. These two drugs were tested on human prostate tumours grown in the laboratory. Blocking fatty acid uptake reduced prostate tumour growth to 40% of untreated tumours. Blocking conversion of carbohydrates alone had a similar effect. Best results came from both drugs together, which slowed tumour growth to only 10% of the untreated tumours.

This research had uncovered a weakness in the prostate tumours that could be exploited by a new treatment approach targeting cell metabolism. This new approach has only been tested on tumours grown in the laboratory, not on humans. Hopefully these exciting findings will lead to a drug development project to attempt a similar approach for humans.

Should we avoid eating fatty acids?

The terms fatty acids refers to many different products found in foods. It includes “good fats” such as omega-3 fats found in nuts and oily fish. It also includes “bad fats” such as saturated fats (found in dairy and meat fat) and trans fats (found in highly processed foods and bakery goods). Eating too many “bad fats” can be bad for your health. It causes obesity and raises cholesterol levels, causing heart disease. Healthy eating guidelines recommend limiting the saturated and trans fats that we consume.

We know that men with prostate cancer who eat higher levels of saturated fats are more likely to see their cancer turn aggressive. PCFA recommends men with prostate cancer limit foods containing saturated and trans fats, in accordance with the Australian guide to healthy eating.

PCFA are proud to have funded this successful project through a Movember New Concept Grant.