New Dawn In Cancer Research

Part 1: Epigenetics in the Puzzle of Cancer

11 min readJan 23, 2024

Have you ever lost someone you love?

I remember my mom and dad coming to my bed when I was 7. Normally, they never come to my bed at night like that; I used to sleep alone. This time, they both came together and lay next to me, hugging me in between.

“We have to tell you something,”

If they came to my bed today and said something like that, I would understand that something bad had happened. But at the age of 7, I couldn’t. I didn’t know the typical way of delivering bad news to someone, approaching gently, hugging, weird silences between phrases… I wasn’t watching many movies back then, so I didn’t have patterns in my mind to identify. In fact, I was pretty happy (I was still having difficulties falling asleep, and my mom and dad came to my bed together, hugging me — heaven!).

“Remember when your fish died,” my mom said.

Apparently (I mean, it’s clear now), they had discussed how to explain that subject to me, and they found this way.

“Yeah,”

I was still angry with my parents about that.

I used to have a lot of fish at that time, and I took good care of them. I changed their water, cleaned the aquarium twice a week, and gave them their disgusting but interestingly colorful food — not too much because they could die if they were overfed, not too little because they could starve. They were so fragile, and I highly paid attention to them to live long and healthy. However, one day when I ran to the aquarium to feed them, one of them was missing. I told my parents, but they looked and said,

“No, you must be mistaken; everyone is there.”

When I was cleaning the aquarium that week, I found the missing one, stuck in a big shell in the aquarium as a decoration, and she was gone. I was so sad to be right — and angry. If they had listened to me and believed me, we could have found her before she died! In my way, I continued to be angry with them for days and didn’t talk to them much, as if it was their fault. I was so sad and trying to find someone to blame. My fish used to live way longer than average, by the way. I realized later that they didn’t generally have a very long lifespan, and I took pretty good care of them. Maybe, when I realized that morning that she was missing, she was already dead — I don’t know. All I knew was I was angry because they didn’t believe me and caused the death of one of my precious fish.

That night, when my mom brought up the matter again, I responded exactly like this:

“Oh, how you didn’t listen to me and caused the death of my favorite fish. (I didn’t have a favorite; she became my favorite after her death.) I do remember.”

You little, silly kid… I discussed that matter at that point, in an unbearable manner. And that night, I learned that my granny died.

I remember I couldn’t understand it. I wasn’t sad like I was supposed to be because I couldn’t understand what that meant. I had no idea that she was ill; all I knew was she had passed an operation, but it went well, and she was doing okay. I hadn’t seen her for a while, and I missed her.

My grandmother was the one who raised me. I’m a child of working parents, and in my country, maternity leave is only 1 year. So, she was the one who looked after me for years until I started school. She was a part of my life, and I couldn’t imagine a world without her. I had started school early and went to kindergarten for 2 years before starting from 1st grade. I didn’t know why back then. Since I started school, I hadn’t been seeing her much, and I knew she finally was living in her house and had passed an operation and… Fine. She was fine.

As the school had replaced her place, and it was so new and exciting to me, I wasn’t aware that something wasn’t right. I had tons of friends, was doing lots of interesting things, and I was living in a wonderland. When my mom said that, I didn’t understand it because even though I didn’t see her, I used to know that she was there, living happily. But knowing that she wasn’t here anymore, I couldn’t understand how…

I can’t imagine how hard it was for my mom to tell me. She had to seem strong and explain the death of her mother to me, an inexperienced 7-year-old, while she was in agony and I was still trying to prove that it was their fault that my fish died.

This was the first time that I felt death so close to me. I’ve always felt so unhappy when my animals died. I grieved when one of my chickens died for days (yes, I used to have a lot of chickens too, taking care of them pretty well, obviously). However, a human’s death, for me, was so different and something new.

I also got used to it over time. I hadn’t seen my grandfather ever. My other grandpa passed away after 2 years that my granny died. My best friend lost her father when I was in middle school. All of them had something in common: cancer.

I’ve never thought about death much, avoiding thinking about it, not bringing it up in my mind at all.

However, my uncle had overcome cancer years ago, and now it has returned. And this time, he is not responding to any of his treatments. And I’m scared. I’m scared of losing him too, I’m scared of the thought of my aunt (the nicest person in the world) losing her husband, and my cousins who are the same age as me losing their fathers.* I’m scared of the thought that something is growing inside of you, killing you. I’m scared that I can be next.

I’m 100% sure that you know someone who died because of cancer or at least someone losing one of their closest because of it. It’s among us and too common.

Estimated numbers from 2020 to 2040, Males and Females, Age [0–85+], All cancers, World | Source

By no means am I going to suggest I have found a way to prevent it completely as a 16-year-old, nor can I say I found a cure. Especially when thousands of extraordinary scientists from all over the world are tirelessly fighting against it. Right now, as a future scientist, I’m in the training stage, to fill their shoes later. What I want to do now, is to share a promising area of cancer research that I believe can open a new door.

*ps. Before even I be able to publish this article, I already lost him.

Quick Explanation: What Is Cancer?

By definition, cancer is a disease in which some of the body’s cells grow uncontrollably, invading other tissues and organs. (1)

There are many different types of cancer, yet each begins when a single cell acquires a change that allows it to divide and multiply unchecked. (1)

Genes That Are Associated with Cancer

When it comes to cancer, there are certain genes that we can’t skip without mentioning:

Oncogenes

An oncogene is a gene that can cause cancer.

Why do we have genes that cause cancer?

Well, normally we don’t have them by birth. What we have is “proto-oncogenes” and they are essential in regulating cell division. The problem occurs when they are mutated, — in that case, we call them “oncogenes”, causing cells to start dividing and multiplying uncontrollably.

You can think of them like the “gas pedal”, pushing cells to divide again and again. (2)

2. Tumor Surpressor Genes

The second type of genes to mention here are tumor suppressor genes. We do have them already in every cell in our body, and they are responsible for keeping cell division under control, or ensuring cells die when it’s necessary.

You can think of them as being like “the brakes” of a car. They’re the ones that stop the cars when oncogenes are pushing the gas pedal. (3)

Normal and Mutated Tumor Suppressor Genes | Source

3. DNA Repair Genes

The last gene group to mention here is DNA repair genes. As their names explain, they are responsible for repairing the mistakes that occur in a cell’s DNA. They make sure that our information is preserved, potentially preventing proto-oncogenes from turning into oncogenes or ensuring tumor suppressor genes function normally. (4)

Now, we’ve known for a long time that genetic mutations, and changes in the DNA, may lead to cancer.

For example:

Mutations are the things that cause proto-oncogenes to turn into oncogenes.
Tumor suppressor genes can be erased because of mutations.
Changes in the DNA repair genes might lead to other mutations and eventually cause cancer.

Therefore, until now studies have generally focused on gene therapies and gene editing techniques to cure cancer. And they have succeeded in some cases, providing promising results.

However, these methods also come with some problems. In addition to that, only a very small minority of cancer cases (5–10%) are due to inherited genetic mutations. (5)

Whereas the vast majority (90–95% of cases) is caused by non-hereditary; environmental, physical, and hormonal factors. (5)

Thus, we’re still pretty far away from being able to say that we have found the cure for cancer with gene therapy.

With that being said, there is another aspect that I want to mention now:

EPIGENETICS

Heard of epigenetics?

If you haven’t, I highly encourage you to check out my previous article where I explain how exactly it works. But anyway, I’ll mention what they are briefly in case you don’t.

Up to this point, you know what “DNA” is already. It’s the code of our life, our bodies, our existence. However, DNA doesn’t mean anything on its own; this is not a single-player game. It works with epigenetics. Epigenetics is the information that “opens” or “closes” specific sequences of our DNA, making some information accessible or inaccessible, responsible for gene expression.

We have a lot of information in our DNA, so much so that if we uncoiled each of our DNA strands and placed them end to end, the resulting strand would be 67 billion miles long — the same as about 150,000 round trips to the Moon. (6)

As we all become complex human beings from a single cell, and that cell divided billions of times and made us as we are, it’s normal that all of our cells have the same information. That’s when epigenetics enters the scene.

It’s what silences the genes that would make your neurons or liver cells while activating the genes that would provide them their identity as a neuron. By turning genes on and off, they ensure differentiation.

Unlike our DNA, this information is not permanent and starts to get lost over time, can be easily affected by lifestyle and environmental factors. This can cause the expression of some genes that shouldn’t be expressed and deactivation of some genes that should be active. Resulting in the loss of identity in our cells, stopping doing their jobs, or even the aging process itself.

Here is an awesome 5 min long video from Ted-Ed explaining Epigenetics

Now that you have understood the basics, let’s get to how this has given us a new perspective on cancer research.

Remember when I said nearly 90–95% of cancer cases are caused by physical and environmental factors?

What does the environment affect if they don’t only cause mutations?

Epigenetics.

And as I said, it’s not permanent. Your lifestyle, habits, and overall health have a huge impact on epigenetic information. So, even though inherited genetic mutations may lead the cancer, it’s just 5–10% of the cases and gene therapies are under development for that. Therefore, your genes are not your destiny.

Now, what if we could alter our epigenetics just like we can alter our genes?

Let me tell you the answer, we could turn off the oncogenes, make sure that our tumor suppressor genes and DNA repair genes are expressed as they are supposed to be and not turned off.

And how it’s gonna happen?

Well, the first thing you can do is to take care of your overall health, having a healthy lifestyle, environment, and diet. However, science has also found some other ways to alter your epigenome in a desired way; ensuring that the genes that should stay silent are silent and the ones whose voices must be heard are expressed.

Some of the methods that are being used in epigenetic alterations are:

CRISPR-Cas9
Small molecule modulators
Nucleic acid-based therapies, such as antisense oligonucleotides and RNA interference (RNAi)
Gene editing therapies, such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs)

Final Thoughts

For decades, cancer research has focused on genetic mutations. I’m not saying it has no effect; a lot of genetic mutations have been associated with cancer, proven by peer-reviewed research, and significant progress has been made in tackling these mutations for those whose cancer is caused by a genetic mutation. However, not every cancer is the same.

Our understanding of epigenetics has only started to be realized over the past decade and is advancing every day. Rearranging what we already have and showing how it used to and is supposed to work again can be a valuable approach. I’m not saying that this was the key, and we have found it; plus, it is also far from being perfect, and questions persist regarding its precision, potential off-target effects, and the lasting impact of the alterations they introduce. The field of epigenetic editing is still in its early stages and comes with its share of challenges and uncertainties.

However, it’s obvious that this was a significant step in seeing cancer as a whole and coming closer to a more holistic approach. And even though it might not be that easy to prevent it at this stage, I’m pretty confident that it can augment the effectiveness of therapies significantly in some cases, maybe preventing a little girl from losing her granny.

In conclusion, while epigenetic approaches offer promise in improving therapeutic outcomes for specific cases, they are not without challenges. The uncertainties associated with epigenetic editing emphasize the necessity for ongoing research, the establishment of ethical guidelines, and a cautious approach in navigating the dynamic landscape of cancer therapy. By thoroughly exploring these challenges and confronting them directly, we can aspire to unlock the full potential of epigenetics in the ongoing battle against cancer.

2 min long video from American Cancer Society

SOURCES: