Transcriber: Mahshid Moballegh Nasery Reviewer: Sadegh Vahdati Nia
Good afternoon.
My name is Sendurai Mani and a professor of pathology lab medicine
and also an associate director for the translational oncology
at Brown university;
Legorreta Cancer Center, Brown university.
Today I am going to walking through
how the cancer originates
and then what can we do to prevent
or get ourselves checked properly?
So before that, I just want to let you know that our body is like
a community where we have more than 30 to 40 trillion cells.
They work together symbiotically.
We have a digestive system which kind of digest the food.
It's like a food processing machinery, cleaning machinery.
And we have all kinds of systems, including an army
to destroy any foreign invaders.
So this slide shows that how in animal Kingdom,
the symbiosis play a vital role in keeping everyone healthy and happy.
Same thing happens in our human body.
So again, we have nearly 30 trillion cells and we also have
a bacteria in our body, which is almost 38 trillion in our human body.
And they all work together.
Unfortunately, cancer is still a major problem.
It doesn't discriminate anyone. It's like a thief.
It penetrates or invades our life.
And steals our health, happiness and our wealth. Everything from us.
It doesn't discriminate whether it's young or old.
It doesn't discriminate whether you are male or female or your ethnicity
or you are rich or poor.
It doesn’t matter. It affects everyone.
So it’s extremely vital for us to understand what it is,
why people do get cancer.
If you understand that better,
it's easier for us to prevent it and diagnose at the right time.
So that slide shows in the world
we have nearly 20 million people diagnosed with cancer in 2020.
And among that,
10 million of them died because of cancer.
In the US, It’s the good news.
“The cancer incidence is dropping down every year.”
This slide shows that you can see that from the top curve,
which shows cancer incidence in male and female.
And in the bottom you see the cancer related mortality.
It’s dropping down, it’s really dropping down.
But we still have quite a lot of cancer related death in this country.
We saved nearly 2.5 million men and 1.5 million women’s live
in the last ten years due to advanced diagnosis,
as well as treatment options.
We will walk in through.
I’ll walk in through most of that in the next few slides.
However, there’s one cancer
we still don’t have a good solution is Pancreatic Cancer.
Here you can see the cancer incidence is going up
and cancer related mortality is also going up both in male and female.
So we need to understand that better.
Moreover, you know, if somebody has a localized disease,
let’s say breast cancer, the survival rate is extremely high, 99%.
But on the other hand, somebody has a metastasis.
So this is a localized disease. If somebody has a metastasis,
or somebody has liver or pancreatic cancer,
again the survival rate is extremely low.
So I’m going to walk you through about three different types of cancer.
The reason is, in the many times people come and ask me,
my uncle has a cancer, my aunt has a cancer, will I get a cancer?
So we need to understand these different types of cancers which exist.
So that you understand whether if somebody has a cancer,
will I get a cancer?
For example, there are three major types,
we call what is called a sporadic,
which happens due to our lifestyle that is called hereditary.
It's due to a mutation in parents or could get transmitted to the progeny.
That’s a hereditary, that’s a familial where
it’s a combination of both hereditary and
the environment where they live in.
The combination together causes the familial cancer.
So before that, we need to understand what is DNA,
what is gene and how people get cancer, if somebody has a mutation
or inherited some genetic defect.
So here you see on the left, you have a cell
and cell has chromosomes, as you could see.
And inside the nucleus and those chromosome is made up DNA
and the DNA makes genes.
My daughter asked me, what is the difference between DNA and genes?
She’s 11 years old.
And so I thought of this example where you think about road in Providence,
all the roads you could call it as a DNA, but within that there is a Smith Street,
which you can see as small stretch of road is called Smith Street.
Same thing.
You have a meter long DNA in each cell,
and a small portion of that DNA is called a gene.
And so now comes how cancer happens in human being.
Just think about a car, okay?
I said we have 30 to 40 trillion cells in human body.
Now each cell is like a car, just imagine.
Now a car has a brake and accelerator and gas.
So brake when you are going fast, you can apply a brake.
When you are not going faster, you can apply an accelerator. You go fast.
When the gas tank gets empty, the car cannot go anywhere.
Same way we have a brake system. It's called a tumor suppressor.
If among this 30 to 40 trillion cells, one cell decide to go rogue,
the brake system works and stops the cell from going rogue.
And but imagine,
somebody has a mutation
in another set of genes, called oncogene.
Then you are constantly pressing the gas, the car will continuously go.
Still, there is one more brake, one more kind of control system, which is a gas.
Once the gas tank is empty, the car cannot go anywhere.
So you have a third set of control.
So in body, we have a clock system which senses how many times SL can divide.
Same way how many years a human can live,
each cell among this 30 to 40 trillion cells has a clock.
It will sense these many times you can divide. Then you need to stop and die.
That’s a programmed cell death.
So that is determined by something called a telomerase, they have a limited cycle.
What happens in cancer?
They turn on an enzyme called telomerase.
They keep adding telomeres to the end. So they don’t stop.
So these are the three major hurdles a normal cell has to gain
to become a cancer cell.
So which is summarized here.
So you need to mutate the tumor suppressor gene,
mutate the oncogene become active,
then have a continuous activation of telomerase to have
almost like a solar powered gas tank, solar powered car.
So you can run on a sunlight as long as you have a sunlight.
So this is kind of puts the cell into a crazy signaling system,
which the cell responds by dividing and creating more cells of themselves
and that end up in tumor.
But you also want to understand this cancer is mostly
age-related disease.
So in other words, most of the time because we live longer,
we tend to accumulate more mutation over a period of time due to our lifestyle.
And that’s what is shown in this slide where you see,
people gaining/getting cancer only late in life.
So this slide shows that if somebody has
a mutation in this tumor suppressor gene,
the genes are also called brake genes
which I was mentioning earlier,
that so those can be inherited from parents to the progeny to the children.
But just because somebody inherits a mutation,
doesn’t mean that they will get a cancer.
Remember, there are three steps
as normal cell has to pass in order to become a cancer cell.
What it means is that if they get a mutation from their parents,
inherited a mutation from the parents,
which means they are prone to get a cancer,
but they are not going to get a cancer.
So here a kid having a retinoblastoma mutation in her blastoma gene.
RBE Gene is developing a mutation.
Tumor in the eye, something APC which is creates a colon tumor.
And then you see on the right, Angelina Jolie.
She had a mutation in a gene called Baraka one,
which is a tumor suppressor GINA, the break gene.
And she decided to go and remove her,
do a mastectomy of both her breast just to prevent cancer from occurring,
not because she had a cancer.
So again, the environmental effect play a vital role.
So pollution, drinking alcohol, stress, stress is a major player.
So take time off. Enjoy your life.
Microbiome, You know, we all take microbiome for granted.
I said there are 38 trillion bacteria in our body, so if you kill them,
they are going to create its own consequences.
So be respectful of your microbiome.
And you know, smoking, eating junk food,
so it also adds to cancer.
So what I have done so when I was at MIT many years ago,
people in the Weinberg lab where I did my research here is
a gentleman in his lab, they found that you can transform a normal cell into
a cancer cell in a laboratory by inactivating the tumor suppressor.
Getting rid of the brake,
having a tumor oncogene and having a telomerase,
they were able to make cancer cells.
So what I found those cancer cells don't go anywhere
because they are epithelial cells attached with one another.
That's what happens. That's why all the cells in our body,
they are attached with one another.
In order for them to go from one place to another,
they need to break this acceleration cell matrix interaction.
Now, they can go anywhere in the body.
That’s called epithelial to mesenchymal transmission.
So in addition, when a pathologist look at a tumor in a lung,
a pathologist could predict that tumor in the lung is coming from breast
or prostate or longer liver,
just because they create a structure very similar to where they come from.
So I hypothesized
that tumor cells not really become
migratory but also become stem cells.
That turned out to be true.
Now targeting cancer stem cells become a major issue
because they are responsible for metastasis,
tumor relapse and treatment resistance.
We are in the process of developing treatment for metastasis.
So until now, you know,
the treatment has been
more just one kind of treatment.
If somebody has a cancer, they used to get one type of treatment,
chemotherapy or some treatment.
Recently, we have invented this precision oncology where you have a patient,
you classify them by sequencing their tumor.
You classify them into group who has a different mutation in their tumor,
oncogene the the accelerator genes.
Now, based on that, we have drugs for each mutation.
So you can give medicine to the patient into different groups and you get
a benefit in among all the three groups.
So this is, for example, an example where a patient had a mutation in
a BRAF gene, which is one of the oncogene.
Now you give a drug which targets that mutation,
the tumor is completely gone and there's a problem which the tumor can relapse.
But that’s another problem which we are in the process of addressing.
Here is Jim Allison who really revolutionized cancer treatment recently.
He found that the tumor cells somehow convinces immune cells not to kill them.
So he found that secret code,
which tumor cells tell the immune cells that I'm your friend.
He went ahead and blocked that signal.
By doing that, he's able to make the immune cells kill the tumor cells.
That is really making a huge impact.
If somebody has a melanoma,
some time ago, we say it’s a death sentence.
No longer the case.
You can really treat them with immunotherapy.
So the future is really bright.
For example, olden days when somebody wants to get a colonoscopy,
colonoscopy for a colon cancer screening, it's very hard.
Now, there's a company here.
They have developed a small camera, which is like a pill you ingest.
It just go through your stomach.
It pictures the whole gut and you get a picture of what happens inside.
There’s another company on the right, Olive Diagnostics developed
a toilet seat where you sit when you are doing what you are doing,
It can kind of capture what is anything wrong in the urine and give you
an information. And you know, there’s another thing called Digital Twins,
which is quite an interesting idea.
So you guys are all constantly feeding data into various companies using
wearables as well as your genomic sequencing and all that.
With that, people are able to create a digital twins of you.
And with that one could predict what kind of medicine you may need.
So here is a company they have announced launch of Gemini, the in Silico patient,
for multiple myeloma. So it's basically digital twins.
The sequencing cost is dropping every day.
It was nearly $100 million when they initially sequenced.
Now it's you can sequence it for 500 to $800 genome.
The goal is now you get the genome or this various information,
feed them into supercomputer,
and that would speed out a proper treatment for cancer patients.
So until now, various experts like a pathologist, clinicians, oncologists,
basic scientists, we all used to work to some extent together,
but not necessarily as a team.
What we are doing here, at the Legorreta Cancer Center
and all over the world is forming
a team, working as a team to target this devil.
So here is a group of the people who are working with me at Brown University
and also the Legorreta Cancer Center.
Again, I hope I'm able to convince you that the future is bright.
It's you know, we have a hope.
And if somebody's cancer is diagnosed early in time,
the survival rate is very high.
So we need to really work together.
So I request all of you to play a vital role in this by participating,
either by supporting cancer research or participating in clinical trials,
or simply by promoting awareness among people
that cancer is not a death sentence.
It’s a curable if it diagnosed early.
So go get proper diagnosis, early diagnosis done.
And thank you all for the opportunity.
(Applause)