When I first watched Li’s TED talk I was a believer in his message that a diet full of anti-angiogenic foods can be an effective way to prevent cancer. However, with a couple of more views, I became less confident in his message and a little disappointed in how he presented a few of his points (which was originally the main aspect of the video I was fascinated with).
If it seems too good to be true…
An example of this is how Li presented the data on patient survival before and after 2004 (graph shown below). In the lead up to the graph, Li shows a bunch of examples of how anti-angiogenesis treatment in various animals led to significant improvements in the tumor size and the animal’s health. This establishes absolute confidence in anti-angiogenic therapy in the viewer’s mind. Because of this, when Li shows us the improved cancer survival time after 2004 (a landmark because it is when anti-angiogenic drugs were approved for treatment) the viewer may attribute the 70-100% improvements solely on anti-angiogenesis. However, the post-2004 data is being compared to “the era in which there was only chemotherapy, or surgery, or radiation available” which could include data from 30 years ago. If we are comparing data that includes the 70s and 80s where early cancer detection, treatment and public awareness are nowhere as advanced as they are now, then the improvements shown in the graph cannot be due to anti-angiogenesis alone. On the other hand, if the pre-2004 data only included data from 2000 onwards, then maybe it could be concluded that anti-angiogenesis is a main player here. As well, how many of the patients used anti-angiogenesis as a treatment method? According to the Angiogenesis Foundation website, 1.2 million people have been treated with anti-angiogenic therapy as of 2008, while the American Cancer Society reports that there were close to 1.4 million new cases of cancer in 2005 alone. Since anti-angiogenic therapy isn’t currently a very common method of treatment, it would be safe to say that unless the post-2004 data was specifically focused on anti-angiogenesis, the majority of the patients would have used a different form of treatment. I feel this way of presenting the data is somewhat misleading, especially if it turns out that any inferences that could be made from this data are irrelevant to the effectiveness of anti-angiogenic therapy.
Which came first, the mutation or the angiogenesis?
As Li explains, most people will develop “cancer without disease” in the form of micro-tumors that are unable to grow due to limited blood supply. But these micro-tumors become dangerous when they mutate and are able to release their own angiogenic factors to create an extensive vessel system that will serve to feed the tumor. Li then states that “angiogenesis is a tipping point between a harmless cancer and a harmful one,” and suggests that anti-angiogenic factors can be an effective form of cancer prevention. But to me, the mutation of the micro-tumor is the tipping point, and the increase of angiogenesis is a fallout of that mutation. So what causes these mutations? Most environmentally-linked cancers are due, in part, to carcinogens (factors that can cause genetic mutation, like alcohol and cigarettes) and free radicals (species that have an unstable electron configuration and take an electron from another compound, making that compound unstable). These can alter the cell’s DNA and cause the activation of cancer-promoting oncogenes, or the inactivation of tumor suppressor genes, found within the cells.
Is there a better way?
Most people try to reduce their risk of cancer by, as Li alluded to, stripping away factors that are known carcinogens (factors that can cause genetic mutation, like alcohol and cigarettes). But many people, as Li promotes, are already choosing to add foods to their diet to prevent cancer. However, rather than conscience consumers looking for angiogenic foods, they look for products with anti-oxidative properties. These dietary factors can alleviate the oxidative stress caused by free radicals, preventing them from damaging the cell. This form of dietary prevention is much more known among the public when compared to anti-angiogenesis, and for good reason in my opinion. The mutation of the tumor, according to Li himself, precedes the expansion of the tumor bloods vessels so if the initial mutation is prevented, then angiogenesis is not an issue.
Lycopene – anti-oxidant or anti-angiogenic?
Near the end of his talk, Li presents an epidemiological study that he claims demonstrates the effect of a diet rich in anti-angiogenic foods on reducing the risk of cancer. It is hard to draw such a direct conclusion from a study this large since there are many other factors that can play a role such as; lifestyle, physical activity levels, do they drink, do they smoke, income, etc. Also, the main component in tomatoes that was of interest in the study was the phytochemical, lycopene. Though Li states that lycopene is a anti-angiogenic, it is much more known for its role as an anti-oxidant. Even in the slide deck created by Dr. Mucci about this study, she emphasizes the tomato/lycopene’s importance in negating ROS (reactive oxidative species, also known as free radicals) and how that action prevents angiogenesis. Though lycopenen can be viewed as anti-angiogenic, its its role as an anti-oxidant that actually helps prevent cancer and is how it is anti-angiogenic.
What is anti-angiogenesis good for?
I don’t want to come across as pessimistic about Li’s work. His work shows great promise as treatment to diagnosed cancers, it just needs more clinical trials to back it up. I am just skeptical about an anti-angiogenic diet as a prophylactic measure against cancer based on how Li was using data and selected studies in a bit of a misleading way.
Can a diet based on anti-angiogenic properties prevent cancer? I’m not sure. I don’t think of it as a first-line of defense against the progression of cancer, that title would probably go to anything that prevents cell genetic damage, like anti-oxidants. However, Li may be on to something when he said that “we are treating cancer too late in the game, when it’s already established.” If the cancer is not diagnosed early enough, it may already have spread. Since anti-angiogenesis shows potential as a treatment to cancer, maybe people at high risk of cancer either due to genetics or age, should be advised to follow Li’s diet plan. That way, if they do end up developing cancer, their altered diet may slow down the progression of the tumor so that it will be much more manageable once it has been detected. This is where I believe Li’s diet can have the most impact, not in preventing the formation of a tumor, but in delaying it’s development.
What do you think?
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.
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.