Apples A Day…

“Can we eat to starve cancer?” – Dr. William Li, Part 1

A new idea that has been getting a lot of attention recently has been anti-angiogenesis, and its potential role in the treatment and prevention of cancer and other diseases. The person who has now become the face of this idea is Dr. William Li, head of the Angiogenesis Foundation. Him and his foundation have been featured on the Dr. Oz Show, Huffington Posts’ list of “Top 10 Medical Events of the Decade”, Bono’s op-ed in The New York Times about the “10 Ideas that might make the next 10 years more interesting, healthy, or civil”, Wired Magazine, O (The Oprah Magazine), CNN, just to name a few. But Dr. Li is probably most known for his talk at TED 2010 entitled “Can we eat to starve cancer?” where Li presents a new way to think about treating cancer and other diseases, anti-angiogenesis –preventing the growth of blood vessels that feed a tumor.

Why this talk?

This talk and of mine through an e-mail thread with about 30 other people on it. This is why I chose to review this talk as my first post. Not only did I find the subject interesting, but I was surprised at its ability to connect with people and is a great example of what I could only dream my presentation skills could be like. Li was not only able present a complex topic like his to an audience who largely are unfamiliar the science of cancer, but was able to convey his research and vision in such a compelling way that activated people to share his message. But what exactly is its message?

Below is a summary of the main points made in Li’s presentation. In this post I will just outline Dr. Li’s points and make a separate post for my commentary.

Angiogenesis – the growth of new blood vessels

Our body has the ability to regulate angiogenesis. In situations when more capillaries are needed in an area, like under a scab after a cut or in the placenta during pregnancy, stimulators called angiogenic factors are released to promote the growth of new blood vessels. When this increase of blood vessels are no longer required, inhibitors to angiogenesis are released and the number of capillaries are pruned back to their baseline level. However when this system becomes defective and angiogenesis is out of balance, a number of conditions can occur (outlined in Fig 1).

According to Li there are 70 diseases, affecting ~1 billion people, which on the surface seem to be different from each other but all share one common feature, abnormal angiogenesis. Cancer is one of them.

Cancer without disease

Cancer starts out as a small cluster of cells not much bigger than a tip of a pen (0.5mm3). Hundreds of these clusters are in, or will develop, in everyone. Autopsy studies of car accident fatalities show that 50% of 50+ year old men and 40% of women over the age of 40 display these micro-tumors in their prostate and breasts, respectively. Despite their prevalence, the size of these micro-tumors is limited to their blood supply and remains harmless due to the maintained balance of angiogenesis. Li’s mentor, Dr. Judah Folkman, termed this as “cancer without disease.

So how does cancer become dangerous?

Danger arises when the cancer cells mutate and are able to release angiogenic factors. When this occurs, the tumor increases its own blood supply and is now capable of rapid growth. Over time, part of the tumor can then break off and use the same vessels that feed it to travel throughout the body and form daughter tumors in other organs.

What causes this mutation? Is it oxidative stress?

Li argues that if “angiogenesis is a tipping point between a harmless cancer and a harmful one,” then cancer can be treated by decreasing the amount of vessels that feed a tumor.

Anti-Angiogenesis – Cancer treatment and it’s role in prevention

Anti-angiogenic therapy selectively aims at the blood vessels that feed the cancer cells. Tumor blood vessels are unlike normal blood vessels in that they are they are poorly constructed. This makes them vulnerable to treatments that target them. Li demonstrates this through examples of a brain and a breast tumor that had lost their network of blood vessels after anti-angiogenic therapy. To further drive home the point, he presents examples of the use of anti-angiogenic treatment on other species, namely dogs, horses and dolphins. All animals displayed either marked improvements or complete recovery.

Figure 2: Patient survival time taken from the era when only chemotherapy was available compared to data taken from 2004 when anti-angiogenic drugs were available.

As shown in Figure 2, there was a 70-100% improvement in survival in some cancers, but not others.

Are these improvements directly attributed to the introduction of A-A treatment? Were there any other breakthroughs in 2004 that could cause this?

Was the pre-2004 data taken from a few years before the introduction of anti-angiogenic drugs or is it from a 30 year period?

Li attributes the lack of improvement to the advanced stage at which the cancer was diagnosed.

Is this the only reason for the non-response?

Are those types of cancers more difficult to diagnose and are typically identified later than the cancers that did show improvement?

As a result of this revelation, Li had decided to shift his attention from anti-angiogenesis in the treatment of cancer to its potential use as a preventative measure for cancer. Since diet attributed 30-35% of environmental caused cancers, which accounts for ~90-95% of all cancers, he looked for what can be added to a person’s diet that is naturally anti-angiogenic.

Li vision for his research is to create a rating system to score foods based on their anti-angiogenic cancer preventative properties. With a list of foods that contain anti-angiogenic factors, as well and known food synergies, recipes could be (and are being created by his foundation) designed as a preventative measure again abnormal angiogenesis-induced disease.

In working towards this goal, Li’s research has focused on identifying foods with anti-angiogenic properties, quantifying their potencies at concentrations that are attainable through diet and identifying which dietary factors exhibit synergistic relationship in terms of their anti-angiogenic potency. However, all of these studies were done in vitro.

Are the bioavailabilities of these anti-angiogenic factors being accounted for in his research?

Noting this, Li presents a patho-epidemiology study of prostate cancer done by Dr. Lorelei Mucci of Harvard School of Public Health. In the study, which included 79, 000 men, it was shown that “Men who consumed 2-3 servings of cooked tomatoes per week have reduced risk for developing prostate cancer by 40-50%.” In the same study, 820 men that did develop prostate cancer, those who ate more tomato sauce had fewer blood vessels feeding their cancer.

Are there results solely due to the anti-angiogenic properties of tomatoes, or are other variables playing a bigger role (where they live, lifestyle, activity levels, alcohol, smoker)?

Anti-angiogenesis as a cure for obesity?

To close, Li talks about obesity and mentions how “adipose tissue is highly angiogenesis dependent,” and that “fat grows when blood vessels grows.” To illustrate this, he explains a mouse study where they A-A treatment was given to a genetically fat mouse. When given angiogenesis inhibitor, the mouse lost weight until it reached the norm weight of a mouse. When treatment was stopped, the mouse gained the weight back.

Conclusion

It is clear that Dr. Li is very passionate about and has great hope for what research in angiogenesis can bring. Not only does he see it as a preventative measure against cancer, but believes it can be used in the treatment of obesity and thus a preventative measure about all the chronic diseases that it brings.

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November 8, 2010 - Posted by | Angiogenesis, Cancer, Obesity

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