Here is the full transcript of oncologist Sendurai Mani’s talk titled “Why Do People Get Cancer, How It Spreads, And How To Prevent It?” at TEDxProvidence 2023 conference.
Listen to the audio version here:
TRANSCRIPT:
Good afternoon. My name is Sendurai Mani and I am 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 walk through how 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 digests the food. It’s like a food processing machinery, a cleaning machinery. And we have all kinds of systems, including an army to destroy any foreign invaders.
So this slide shows how in the animal kingdom, symbiosis plays a vital role in keeping everyone healthy and happy. The same thing happens in our human body. So again, we have nearly 30 trillion cells and we also have bacteria in our body, which is almost 38 trillion in our human body, and they all work together.
The Impact of Cancer
Unfortunately, cancer is still a major problem. It doesn’t discriminate against 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.
Cancer Incidence and Mortality Rates
In the US, it’s 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 deaths in this country.
We saved nearly 2.5 million men and 1.5 million women’s lives in the last ten years due to advanced diagnosis, as well as treatment options. We will walk through – I’ll walk through most of that in the next few slides. However, there’s one cancer we still don’t have a good solution for: 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, if 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.
Types of Cancer
The reason is, many times people come and ask me, “My uncle has cancer, my aunt has cancer, will I get cancer?” So we need to understand these different types of cancers which exist, so that you understand whether if somebody has cancer, will I get cancer?
For example, there are three major types: we call what is called sporadic, which happens due to our lifestyle; that is called hereditary, it’s due to a mutation in parents that could get transmitted to the progeny; that’s hereditary, that’s 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 a 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 the cell has chromosomes, as you could see inside the nucleus, and those chromosomes are made up of 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 roads in Providence – all the roads you could call DNA, but within that there is a Smith Street, which you can see as a small stretch of road 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 beings. Just think about a car, okay? I said we have 30 to 40 trillion cells in the human body. Now each cell is like a car, just imagine.
Cell Division and Cancer
Now a car has brakes, an accelerator, and gas. So when you are going fast, you can apply the brakes. When you are not going faster, you can apply an accelerator and 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 these 30 to 40 trillion cells, one cell decides to go rogue, the brake system works and stops the cell from going rogue. But imagine, somebody has a mutation in another set of genes, called an 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 gas.
Once the gas tank is empty, the car cannot go anywhere. So you have a third set of control. In the body, we have a clock system which senses how many times a cell can divide. Same way how many years a human can live, each cell among these 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 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.
Requirements for Cancer Development
So which is summarized here: you need to mutate the tumor suppressor gene, mutate the oncogene to become active, then have a continuous activation of telomerase to have almost like a solar powered gas tank, a solar powered car. So you can run on sunlight as long as you have sunlight. So this kind of puts the cell into a crazy signaling system, which the cell responds to by dividing and creating more cells of themselves and that ends up in a tumor.
But you also want to understand that cancer is mostly an age-related disease. So in other words, most of the time because we live longer, we tend to accumulate more mutations over a period of time due to our lifestyle, and that’s what is shown in this slide where you see people 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 – 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 cancer. Remember, there are three steps a 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 cancer, but they are not going to get cancer.
Examples of Inherited Mutations
So here a kid having a retinoblastoma mutation in her blastoma gene, RB1 gene, is developing a mutation, a tumor in the eye, something APC which creates a colon tumor. And then you see on the right, Angelina Jolie. She had a mutation in a gene called BRCA1, which is a tumor suppressor gene, the brake gene. And she decided to go and remove her — do a mastectomy of both her breasts just to prevent cancer from occurring, not because she had cancer.
Environmental Factors Contributing to Cancer
So again, the environmental effect plays 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 their own consequences. So be respectful of your microbiome. And you know, smoking, eating junk food, so it also adds to cancer.
Research on Cancer Development
So what I have done – 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 was those cancer cells don’t go anywhere because they are epithelial cells attached to one another. That’s what happens. That’s why all the cells in our body, they are attached to one another. In order for them to go from one place to another, they need to break this cell-to-cell matrix interaction.
Now, they can go anywhere in the body. That’s called epithelial to mesenchymal transition. So in addition, when a pathologist looks at a tumor in a lung, a pathologist could predict that the tumor in the lung is coming from breast or prostate or lung or liver, just because they create a structure very similar to where they come from.
Cancer Stem Cells and Metastasis
So I hypothesized that tumor cells not only really become migratory but also become stem cells. That turned out to be true. Now targeting cancer stem cells has 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.
Precision Oncology
So until now, you know, the treatment has been more just one kind of treatment. If somebody has 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 groups who have different mutations in their tumor, oncogenes – the accelerator genes.
Now, based on that, we have drugs for each mutation. So you can give medicine to the patient in different groups and you get a benefit 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 oncogenes. 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 convince 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 melanoma, some time ago, we would say it’s a death sentence. No longer the case. You can really treat them with immunotherapy.
Future of Cancer Diagnosis and Treatment
So the future is really bright. For example, in the olden days when somebody wants to get a colonoscopy for 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 goes 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, that developed a toilet seat where you sit when you are doing what you are doing. It can kind of capture if anything is wrong in the urine and give you 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 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 the 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 per genome. The goal is now you get the genome or this various information, feed them into a supercomputer, and that would speed out a proper treatment for cancer patients.
Teamwork in Cancer Research and Treatment
So until now, various experts like pathologists, 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.
Conclusion
Again, I hope I’m able to convince you that the future is bright. It’s, you know, we have 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 curable if diagnosed early. So go get proper diagnosis, early diagnosis done. And thank you all for the opportunity.