Dear Friends,
It has been ever so long
since I have sat down to write to you. My world has become incredibly busy,
since the last time I wrote to you. I am at a crucial point of my life, with
one year of school remaining and another six years of University life to look
forward to. Many of you may be in such a position, in which case, I wish you
all the best of luck for the future (not that you're going to need it). I will
try desperately hard not to make this post very long, but I can't make any
definite promises.
So, I guess I'll introduce
the background behind this seemingly strange title. Fairly recently, I have
being doing some super-curricular research and reading into various topics in
medicine that interest me. Whilst browsing through a list of TED Talks, I came
across one given by a Dr William Li (who in fact heads the Angiogenesis
Foundation). His concise and coherent explanation of the role of angiogenesis
in tumour growth sparked some curiosity in me. Why hadn't I heard about this before?
I mean Chemotherapy, Radiation Therapy and Surgery were fairly well known
conventional treatments. We had already learnt about these various approaches in
Biology lessons and through our general reading. Maybe I have been behind in my
knowledge of advancements in cancer treatment, but the use of antiangiogenic
drugs was completely new to me. So, I decided to investigate. (It has been a
bit of a learning curve for me, so I will share exactly what I have learnt with
you, as well. That way, it helps to solidify my knowledge and will probably
make sense to you.)
I think we should start by
understanding what the process of angiogenesis entails. According to Wikipedia (http://en.wikipedia.org/wiki/Angiogenesis),
angiogenesis is defined as the "physiological
process through which new blood vessels form
from pre-existing vessels". Blood vessels come in three distinct varieties,
arteries, veins and capillaries. They are comprised of cells called endothelial
cells. In fact, the total surface area covered by these cells amasses to a
total of 1000m2 (in adults). If all the blood vessels in the
body were to be lined up, end-to-end, they would form a line that could
potentially circle the Earth twice. The three types of blood vessels have their
own unique role in the body. Arteries are blood vessels that carry blood away
from the heart, whereas veins carry blood to the heart. Capillaries connect
these two major blood vessels; they are much smaller in size and enable the
actual exchange of water and other chemicals between the bloodstream and
neighbouring tissues. There are an estimated 19 billion capillaries in the body
and they are in essence the vessels of life. Overall, blood vessels have
developed the invaluable ability to adapt to the environment that they’re
growing in. For an example: in the liver these vessels form channels to enable
the detoxification of the blood, in the lungs they line the alveoli to promote
efficient gas exchange and in muscles they form a corkscrew shape which allows
the muscles to contract without the risk of cutting off any vital circulation. Angiogenesis
surrounds the growth of new capillary blood vessels in the body, which is
an extremely important natural process for healing and reproduction.
Diagram of blood vessels in the liver |
Blood vessels surrounding the alveoli in the lungs |
Blood vessel network in a healthy heart muscle |
Diagram of endometrium |
Human embryo attached to placenta |
Insufficient angiogenesis
|
Excessive angiogenesis
|
Chronic
wounds
|
Cancer
|
Chronic
heart disease (CHD)
|
Blinding
diseases
|
Peripheral
arterial disease
|
Psoriasis
|
Stroke
|
Arthritis
|
Neuropathies
|
Endometriosis
|
Pre-eclampsia
|
AIDS-Kaposi
sarcoma
|
Hair
loss
|
Alzheimer’s
disease
|
Obesity
|
|
Multiple
sclerosis
|
|
Cerebral
malaria
|
|
Rosacea
|
As you might be able to guess from the title, I am going to be focusing
on the link between cancer and excessive angiogenesis. As many of you probably
know already, cancer is defined as “a condition where cells in a specific part
of the body grow and reproduce uncontrollably”, according to the NHS (http://www.nhs.uk/conditions/Cancer/Pages/Introduction.aspx).
The danger is that these cells may spread, invade and destroy surrounding
healthy tissue and thus conquer the entire organ, or spread to other organs in
other parts of the body. But it must be acknowledged that cancers don’t begin as
huge clusters of cells with an active blood supply. They are initiated as small
microscopic nests of cells that only grow to approximately 0.5mm3
(i.e. the size of the tip of a ballpoint pen). They cannot expand in size,
without a blood supply that provides the necessary oxygen and nutrients to the
rapidly dividing cells. Moreover, we are probably forming these microscopic
cancers all the time in our body. Autopsy studies that have been carried out on
those who have passed away in car accidents show that around 40% of women
between the ages of 40 and 50 have microscopic cancers in their breasts, and
50% of men between the ages of 50 and 60 have micro-cancers in their prostate.
In all honesty, by the time we reach our 70s, virtually 100% of us will have
micro-cancers in our thyroid gland (one of the largest endocrine glands).
Properly functioning angiogenesis will prevent blood vessels from
feeding the cancers, which is considered one of the most important defence
mechanisms against cancer. But, once angiogenesis to cancerous cells occur, the
cancers can theoretically grow exponentially (which is how cancer changes from
harmless to deadly). Essentially, cancer cells mutate and gain the ability to
release several angiogenic factors that act as a form of ‘natural fertiliser’
that can favour the cancers by allowing the blood vessels to invade and supply
the necessary nutrients and oxygen. Once blood vessels succeed in invading, the
cancer can expand and invade local tissue. The same vessels that are nourishing
the tumour will also allow cancer cells to enter into the circulation as
metastases. Unfortunately, cancers are generally diagnosed at this late stage,
where the cancer is no longer localised and cannot simply be removed surgically
from one place.
A diagram of the progression of cancer |
Angiogenesis-based medicine aims to restore the body’s natural control
over the growth and decay of blood vessels by using innovative medical
treatments. Thus, doctors are able to prolong the lives of cancer patients,
avoid the need for limb amputations, overcome vision loss and improve their
patients’ general health. As mentioned earlier, cancerous tumours release
‘angiogenic growth factors’ that encourage blood vessels to grow into the
tumour. A key mechanism of the proposed antiangiogenic therapy is to interfere with
the process of blood vessel growth by attempting to deny the tumour of the
blood supply that it has recruited. According to the organisation ‘The
Angiogenesis Foundation’ (http://www.angio.org/learn/angiogenesis/),
some cancer patients have experienced positive and dramatic changes to the rate
of growth of their tumours due to the antiangiogenic therapy they have
received. In total, more than $4 billion have been invested in the research and
development of these medicinal drugs, making this project one of the most
heavily funded areas of medical research in history.
Looking back, Dr. Judah Folkman and Dr. Henry Brem discovered the very
first angiogenesis inhibitor molecule in 1975. Following this ground-breaking finding,
the first successful treatment of an angiogenic-dependent disease took place in
1989. This involved the drug interferon alfa2a (an inhibitor) and was used to revert
growth of abnormal blood vessels in the lungs of a boy with a benign disease
called pulmonary hemangiomatosis.
I think it’s important to realise that antiangiogenic therapy is
completely different from conventional chemotherapy, because it ‘selectively
aims’ at the blood vessels that are feeding the growing cancer. This is possible
because the abnormalities that are presented in these blood vessels decrease
the quality of their construction and make them highly vulnerable to treatments
that target them directly. The following table contains a list of the current
FDA approved antiangiogenic drugs, their year of discovery and the list of
cancers that they claim to treat.
Dr. Judah Folkman |
Dr. Henry Brem |
Year
|
Drug name
|
List of cancers
|
2004
|
Avastin
|
Colon,
lung, breast, brain, kidney
|
2004
|
Erbitux
|
Colon,
head, neck
|
2004
|
Tarceva
|
Lung,
pancreatic
|
2005
|
Endostar
|
Lung
|
2005
|
Nexavar
|
Kidney,
liver
|
2005
|
Revlimid
|
Multiple
myeloma
|
2006
|
Sutent
|
GIST
(Gastrointestinal stromal tumour), kidney
|
2006
|
Thalomid
|
Multiple
myeloma
|
2007
|
Torisel
|
Kidney
|
2009
|
Affinitor
|
Kidney
|
2009
|
Votrient
|
Kidney
|
2009
|
Palladia
|
Mast
cell tumours (canine)
|
According to Dr. William Li, the President and Medical Director of the
Angiogenesis Foundation, the use of antiangiogenic drugs have resulted in some
drastic cancer survival improvements in some cancers. For an example: The
survival rates for metastatic kidney improved by 92%, multiple myeloma showed
improvements of 70%, metastatic colorectal cancer sufferers had an improvement
of 92% and those suffering from Gastrointestinal stromal tumours (GIST) had an
improved survival rate of 106%. But, he began to question why other cancers did
not respond as well. And he came to the resound conclusion that doctor’s and
patients both were noticing, diagnosing and treating cancer too ‘late in the
game’; when it has often already metastasised and spread to other regions of
the body.
As you can see, the largest sector of this pie chart is occupied by
dietary factors. So, the ultimate question that Dr. Li aims to answer is this… “Can we eat to starve cancer?” I
suppose it’s a legitimate question if we acknowledge the fact that several
foods that we consume on a daily basis contain these antiangiogenic factors
that are so vital in preventing cancer growth. Here is a list of some of the
naturally occurring inhibitors of angiogenesis:
Green tea
|
Red grapes
|
Lavender
|
Strawberries
|
Red wine
|
Pumpkin
|
Blackberries
|
Bok Choy
|
Sea cucumber
|
Raspberries
|
Kale
|
Tuna
|
Blueberries
|
Soy beans
|
Parsley
|
Oranges
|
Ginseng
|
Garlic
|
Grapefruit
|
Maitake mushrooms
|
Tomato
|
Lemons
|
Liquorice
|
Olive oil
|
Apples
|
Turmeric
|
Grapeseed oil
|
Pineapple
|
Nutmeg
|
Dark chocolate
|
Cherries
|
Artichokes
|
Others
|
To build on these findings, researchers attempted to discover the
different potencies within the variety of strains of food that they were
experimenting with, which would allow them to create a new food rating system
based on how well each food or beverage scored for their antiangiogenic,
cancer-preventing properties. When these potent concoctions of food and
beverage were analysed against some of the more common cancer-reducing drugs
(e.g. statins and non-steroidal anti-inflammatory drugs), the dietary factors
in some cases were more potent than the drugs. Let’s take tomatoes for an
example. They contain a chemical known as Lycopene. Lycopene is a red pigment,
which belongs to the carotenoid family and is commonly found in fruits and
vegetables that bear that colour. New research suggests that lycopene intake may
have some added benefits to the body. It is considered a great antioxidant and
on top of this it’s the most abundant nutrient of the carotenoid family that
relates to prostate health in men. For further prevention, a higher intake of
lycopene has shown to help lower the risk of prostate cancer. As discovered by
the Angiogenesis Foundation, Lycopene is in fact antiangiogenic, which may
explain its preventative properties. Additionally, Dr. Lorelei Mucci from the Harvard
School of Public Health has confirmed “Men who consume 2-3 servings of cooked
tomatoes per week have a reduced risk of developing prostate cancer by 40-50%.”
Chemical structure of lycopene |
In conjunction with this, further research carried out on various
vitamins (including A and E, beta-carotene, lutein and lycopene) demonstrated
that higher levels of these nutrients in the body provided significant protection
against breast cancer. However, as always, scientists have to turn to their
trusty lab animals to carry out their early experiments and often the results
seen may not apply to humans. Having said that, in mice lycopene has shown to
protect against the development of breast tumours and on-going research is
showing that these nutrients may also benefit those suffering from lung cancer.
So, what can we actually make of this information? Stripping it back to
the dietary factors makes it seem much easier for you and I to improve our
health and our body’s protection against these cancers. For some, ‘dietary
cancer prevention’ may be the only practical solution available. Not everyone
has access to good cancer treatment in terms of radiotherapy and chemotherapy,
so starting at a young age and trying to prevent the formation of large tumours
may be a good idea for all of us. It is estimated by the Angiogenesis
Foundation that “at least 184 million patients in Western nations will benefit
from antiangiogenic therapy and an approximate 314 million patients will
benefit from pro-angiogenic therapy. So I suppose, we should all back-up and
support the research that is currently being carried out by the Angiogenesis
Foundation, because at some point in our lives we may all benefit from the
results of their research.
Once again I must thank the Angiogenesis Foundation and Dr. Li for their
inspiring and informative approach to the topic of angiogenic therapy. I am
deeply indebted to the website http://www.angio.org and the TED Talk “Can we eat to starve cancer?” given by Dr. Li. Please feel
free to check it out at http://www.ted.com/talks/william_li.
So, I suppose that’s the end of this blog post, now you all know just as much
as I do about the topic of angiogenesis and its potential to become a new
alternative therapy for cancer. I apologise for such a long post, I don’t mind
if you stop reading halfway, I only hope that this will raise awareness of the
potential of antiangiogenic therapy. Thank you for reading.
Adios xxx
Wrote by Kyawijewardena