Cancer’s worst enemy is a healthy body microenvironment | Adriana Albini | TEDxVarese

Cancer’s worst enemy is a healthy body microenvironment | Adriana Albini | TEDxVarese


Translator: Zsuzsa Viola
Reviewer: Rhonda Jacobs Imagine the future. The future is for me a life
without cancer in a healthy body. I’m going to talk about
the tumor microenvironment, and to tell you
what a microenvironment is, I’m going to explain that for a long time cancer research has been focusing
mostly on the cancer cell. So, it is a cell that is mutated
in the organism, and it starts proliferating. And this cell has some genetic mutation
and has been studied as a single entity. But this cell is not alone,
it is in our body, which is mostly healthy,
and it lives in an environment. So I’ll make you
think about environment. There are different environments, and our feelings
in different environments change. This is, for instance, the sea. Then here you can see a more
dramatic environment, the mountains. And here is the countryside –
more feel peaceful. And the cancer cell somehow
is surrounded by an environment, and it is different, it changes according [to] how
the environment changes. So this is the story
of a little cancer cell that starts in a healthy epithelium,
and it gets mutated. The mutated cell starts growing,
and it stays very small, and eventually dies as a little tumor if there is no interaction
with the environment. And the tumor environment,
since it is small around the tumor, is called “microenvironment,” and it is made by the healthy
cells of our body, for instance, the inflammatory cells,
immune cells, endothelial cells that make blood vessels, fibroblasts. And the idea, that to interact
[with] the organism is that our body
is corrupted by the cancer and starts helping cancer growth. And the idea of the future
is to help to shape the body to fight the cancer from inside. So the first thing that has been studied
in the microenvironment is the ability of a tumor cell
to stimulate vessels, our transport of blood, to bring nutrition to this initial
transformed group of cells. This is called “angiogenesis.” And basically what you see,
it’s a small tumor; it’s able to recruit capillaries
from existing blood vessels, and through piracy of capillaries,
it starts to get nutrition and also the capability
to go around the body and metastasize. So therapies have been developed from initial studies of, for instance,
Judah Folkman or Gulino to fight angiogenesis, and many drugs have been developed
that are used now actually for cancer, for instance, colorectal cancer, to fight the angiogenesis. And so what happens
is that we can suffocate the tumor, we can avoid that the tumor gets food,
and so this is basically starving it. And this is the first action
against the microenvironment. We can also address this in prevention. This is what the research
of myself and a group has done, trying to prevent this early so to avoid that the tumor
can make those blood vessels. But the microenvironment, as you see,
for instance, in the mountains, or in the woods, is not only one cell, it’s not only endotheliel cells,
but is many, many inhabitants. And you can see,
for instance, in this cartoon, that there are many inflammatory cells, macrophages, neutrophils, mast cells. There are fibroblasts; there are normal,
non-transformed epithelial cells. This is from a review article. And all of those somehow are in the tumor, and they can cooperate with the tumor. So these are eventually all target cells. So, to imagine again,
the environment of the tumor. This is the tumor cell, and those are lymphocytes
that should kill it. But they don’t. When the tumor is able
to teach them to be allies instead of enemies. Why does this happen? Because our good cells
are somehow induced by the tumor cells to became bad cells and help the tumor. And this is called, with immune
[inaudible] cells, “polarization.” So we have macrophages 1,
which are good, anti-angiogenic, anticancer, and there are macrophages M2 that somehow are able
to help the tumor grow. This happens because the tumors
don’t invent anything, they use what is in our,
somehow, history, genetic history. And this is the principle
of wound healing. When there is damage,
when our body is hurt, the lymphocytes run to help,
to fight the enemies, to fight the wound, the damage. And then they recruit other immune cells, the neutrophils, macrophages,
such immune cells. And then when they fought the enemies, they have to build new tissue,
to make the scar. And so there is this phenomenon
that makes the cells grow. And the tumor cell
has a similar mechanism, so there is a wound, basically,
that does not heal. So we came to the idea with Michael Sporn, which is one American investigator
very known for inventing prevention, to use the microenvironment
of the tumor as a target to help our body to fight
the tumors from inside. We also discovered, with our team, in particular with a young
investigator, Antonino Bruno, because imagine the future
is also the young scientist, and with my husband, Douglas Noonan, who is a professor at Insubria,
University of Varese, that there are certain cells –
they’re called “natural killer.” So the killer natural
should attack the tumor cells, but we discovered that in tumors,
some of those cells are polarized, so they help the tumor growth. They don’t kill the tumor cells;
they’re not able to do it anymore. But they feed them;
they make them grow faster. And so those cells we can try
to reeducate to be good guys and help fight the tumor. How we can do this? These are inflammatory cells, so the epidemiology has shown
that using anti-inflammatory drugs can somehow fight inflammation,
also prevent the tumors. A very simple, very cheap drug
that has been able to do this is aspirin. There are a lot of reports that show that people taking aspirin
every day have less cancer. And so also an interesting thing, that aspirin derives from a molecule
from nature, from plants. This is salicylic acid
from the willow tree. And there are many plant
phytochemical derivatives that are able, somehow,
to prevent the tumor. What is prevention? What is chemoprevention? This has been defined by Michael Sporn,
that I mentioned before, a mentor, a collaborator: “The use of specific agents to reverse, suppress or prevent the carcinogenic
process to invasive cancer.” Now we can make many aspirins
from plants, in particular from the diet, from food derivatives. This is very interesting because we know that our diet
can help us stay in good health. So I’m a chemist, originally,
and in the plants we can find, for instance, genistein from soy,
silybin, quercetin from apples, resveratrol from red wine,
epigallocatechin gallate from green tea, and then for instance curcumin
from spices, from curry. Also retinoids, for instance,
lycopene from tomatoes, beta carotene from apricots or carrots. These are all good molecules
that can help our body to stay healthy and avoid that our good cells
become bad and help the tumor. This is a new field –
has been around for a few years. It’s called “nutraceutics.” What is nutraceutical? You can see here a pill
with fruits and vegetable inside. It is a term derived from
“nutrition” and “pharmaceutical.” This term is applied to products
that are isolated from foodstuff, and besides being nutritional,
it can be also of therapy. And there’s another term,
which is functional food, which is a food that besides being
for life, for nutrition, is also good for medical purposes. We have done many
investigations in the field. I have over 330 publications,
and many are on this topic, and the recent study
has been on beer hops. Why beer hops? Because, you know, that it helps transport
beer in a good of state of health adding the hops. The hop so also gives the bitter flavor,
it is very fashionable, but it’s also something good
to protect beer from going bad. And so, as for many other plants,
we can isolate principles and use them. And we have studied one polyphenol,
antioxidant, anti-inflammatory from beer, which is called “xanthohumol.” And as a chemist, in collaboration
with other chemists at University of Pisa with our Armando Rossello and team, we made a modification, like it has been done
from salicylic acid from the willow tree, and made new xanthohumols
there are more bioavailable that can become some sort
of aspirin from beer. So this is something
that we can use to make a drug, possibly low toxic, from nature. Also, another study that we do is,
for instance, from a waste product. You know that olive oil is a product
of the Mediterranean diet, which is very good for our health. But polyphenols are mostly soluble, so when we make the oil,
we throw away with the water a lot of very good principles
for our health. So in a collaboration
with a factory in Tuscany, we have made extracts
from the waste waters from oils. You know, when you make the oil, you throw away the water parts,
and this is also a problem for nature because you have to discard them. We can filter, we can concentrate, and make some functional food
from the olive waste. And this is a very cheap [way to get]
polyphenols, and we’re studying now. And both those discoveries
have been patented, and they can become
products for the future. Also, when we do prevent early,
we can use low-toxic compounds. So just, for instance,
caloric restriction, dietary factors. This is a study that we published
in Nature Reviews Clinical Oncology with an American friend, William Li, that we can use dietary derivatives
to prevent angiogenesis, and the earlier you start,
the less toxic molecules you can use. When the tumor starts advancing, then you have to use
a lot of more toxic drugs because you have a larger mass to fight. Now, so prevention is quite a new concept,
which is called “interception.” So the cancer you can avoid to have it,
but when it’s already running, you can intercept,
just block it there as it is. And many of things that you can do
just avoiding expensive drugs is to try and not get cancer. And these are the things that one can do: Do not smoke. Keep weight in a healthy range. Drink little alcohol. Try to get nice food
like fruits, vegetables, good drinks, fruit juices, spices. Avoid infections. Exercise. Sport is very important. You can prevent cancer
just by doing long walks. And watch your environment, and get regular,
evidence-based screening. And this is Prevention Interception, a publication with Andrea deCensi,
Alberto Costa and Franco Cavalli. So going to the end, basically, a cancer
is a conspiracy of “good guys” turned bad. The microenvironment
can be “chemoprevented” from helping the tumor
to grow and progress. So we can keep
our microenvironment healthy by doing exercise, getting low-toxic drugs,
anti-inflammatory, or eating a very good
Mediterranean diet, for instance. And so this is my vision for the future,
a nice environment, you can be here and dream
of a happy and healthy life, and also you can help these immune cells, and there are a lot
of recent therapies in immunology to reevaluate the potential
of immune cells, and these cells in the environment can
fight the tumor, and avoid that it grows. So the future for me
is having a healthy body, fighting a cancer or actually preventing
that the cancer ever starts. Thank you. (Applause)

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