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Chapter 2

The Biology of Cancer

To understand the basics of cancer treatment, you need to understand the biology of cancer. With this goal in mind, we’ll review some basic human and cell biology to help you grasp cancer’s behavior. Don’t worry; we’ll keep the science at a sixth- to eighth-grade level. Cancer plays by its own rules, and we’ll outline some of these rules as we go.

How a Normal Cell Behaves

Cells are the building blocks of our bodies. Each cell has a nucleus (the center of the cell) that stores the DNA, the “brain” of the cell. The DNA stays in the nucleus, giving out orders.

DNA stores the instruction manual for each one of us. The DNA needs to convey that information to other parts of the cell, so pieces of those instructions are transcribed, or rewritten, as RNA. The RNA exits the nucleus, and the RNA’s instructions are used to build proteins in the rest of the cell. Proteins then perform the actions of the cell. In short, the information is copied and used in this order:

DNA → RNA → protein

The goal of the DNA is to get the instructions to the protein to carry out actions around the cell. These actions could include instructions to grow, divide, sleep, or anything in between.

Each of our normal cells has a program to tell it to stop growing and die when too much damage occurs to the genetic code (the DNA). This process of self-destruction is known as apoptosis. Cancer cells lack the normal signals telling them to self-destruct.

The process is much more complicated than this, but this explanation gives you a framework for how cells work. You can find the biological definitions of DNA, RNA, and proteins in the glossary at the back of the book.

My Mom Had Cancer . . . Will I get Cancer?

Many patients and family members want to know about their genetic risk of getting cancer. If their mom or dad had cancer, will they definitely get cancer?

Most cancers that occur are random events. They come from a mix of risk factors, like age and exposures in the environment such as smoking. (If you’re smoking, please stop! See chapter 12, on nutrition and lifestyle, for help.) For many cancers, there is likely some genetic component underlying its development. However, it’s only a small part of the risk compared to lifestyle, age, and other factors.

There are genetic syndromes, passed down from parents that increase the risk of getting cancer. These genetic syndromes are rare. Still, they do put people at risk for cancer at a much higher rate. Patients may inherit these risks from mom or dad. An example is a mutation in the genes BRCA1 and BRCA2 that increases the risk for breast cancer and other cancers.

To avoid cancer, some patients with genetic syndromes decide to have organs taken out before cancer develops. Patients with BRCA1/2 mutations may have both breasts and ovaries removed to significantly reduce that risk. This is because these patients are at very high risk of getting a cancer of these organs.

If you or someone you love has multiple family members with cancer, please discuss this with a doctor. By talking to a doctor, you can help make sure you or a loved one get referred for proper genetic testing. Identifying these genetic syndromes may be important for a cancer patient’s siblings or children. A patient should work out a complete family health history before meeting with a cancer doctor.

The Cancer Cell: Making Crazy Decisions

Mutations are what drive cancer. They may come from a random event or damage from the environment. These mutations drive certain behaviors in cancer cells that are unusual.

Imagine that DNA is someone who owns and runs a company. What happens if the owner comes to work not thinking right? Maybe they got bonked on the head and have a concussion or amnesia. In some way, the owner has changed their thinking. Their thinking has mutated.

The owner keeps handing down instructions that don’t make good sense to the company’s managers. Still, the managers pass on those instructions to the employees, who act on them.

This change in thinking corresponds to a mutation in the DNA of a cancer cell. The DNA gives inappropriate instructions to the RNA, which uses them to make the proteins that act throughout the cell.

In the rest of this chapter, I outline the core behaviors of cancer. If you want a technical explanation, check out the paper by Douglas Hanahan and Robert Weinberg listed in the resources at the end of this book.

Business Partners: Keeping the Owner in Line

When cell growth gets out of control, the body has a few systems in place to stop it.

Again, imagine the DNA of a mutated cell as the owner of a company, who’s suffering from amnesia after getting hit on the head. So the owner tells the managers to open new stores or to order more inventory, even though the company doesn’t have enough money to do that. Luckily, the owner’s business partners will try to stop, or suppress, the owner from making these big mistakes. They try to put the brakes on the owner’s awful decisions. There are checks and balances in a company to keep it operating smoothly.

There are checks and balances in a cell as well. For example, tumor suppressors stop the cell’s signal to keep growing. Just like the name implies, they suppress or stop tumors from forming. The most well-known tumor suppressor, p53, is known as the “guardian of the genome.”

Kicking Out the Business Partners:
The Cancer Takes Charge

The business owner in our example doesn’t realize anything is wrong! It’s annoying having the partners mess with their work. Therefore, the owner gets rid of the partners and runs the company alone.

Now that the partners are gone, there’s no one to stop the owner. The owner is clear to keep handing instructions down the chain of command.

In cell terms, the cancer cell gets rid of the tumor suppressors. This may be done through mutations. Once the cancer finds ways around the tumor suppressors, it’s free to do what it wants. This allows the cancer cell to focus on growing and dividing.

This is the basic process of cancer growth.

Cancer Orders In: Gorging on Sugar

For cancer cells to keep on growing, they need nutrients: sugar and oxygen (just like the rest of us). To help bring in extra supplies, cancer cells demand that the body form new blood vessels directed to the cancer. These vessels bring in sugar and oxygen.

The cancer cell uses sugar in an inefficient way. Because the cancer cell constantly needs energy, it must bring in and use lots of sugar—an endless process. In biology, this idea is called the Warburg effect (see glossary).

When looking for cancer cells, we use the Warburg effect to our advantage. A PET scan involves tracking a labeled sugar that is taken up by cancer cells. The labeled sugar shows up on our scans, helping us see where cancer may be located throughout the body.

I discuss PET scans in chapter 3, on diagnosis. Chapter 12 discusses whether cancer patients should avoid sugar in their diet.

Not Knowing When to Stop

Normal cells in your body have self-control. For example, if a normal cell senses damage to its DNA, the cell hits the stop button—it stops growing. This is called cell cycle arrest.

A cancer cell is like someone with a drinking problem that keeps getting worse. Each opportunity for the cell to divide is like another drink. These cells don’t know when to stop. Even if they’re sick or broke, they always ask for one more round. As cancer cells grow, they don’t care about damage or other tissues; all they care about is the chance to keep dividing. And just as continuing to drink can further hurt someone’s thinking, mutations can lead to more mutations and instability in the cell. More mutations may give cancer cells more advantages to grow over time.

The Unwelcome Houseguest: Cancer Moves In

If cancer stayed in one place, it would be way less scary. Unfortunately, cancer finds ways to move from one part of the body to the next. This movement is known as metastasis.

When trying to understand metastasis, think of cancer as an unwelcome houseguest. It invades your personal space, taking up precious resources like food without bringing anything positive in return.

The unwelcome guest crashes on the couch, eats all your food, and then asks for more! As cancer spreads to almost any part of the body (say, a bone or organ), it keeps on growing and dividing. There is no signal telling it to stop. Because of this, the cancer may interrupt the normal function of an organ or that part of the body. This is what makes cancer lethal.

Not all cancers are likely to spread. For example, many types of skin cancers rarely metastasize. Tumors that don’t spread may meet the definition of cancer (unchecked cell growth) but are much less likely to cause death.

Cancer Cells Don’t Age

As we grow older, we get wrinkles and show signs of time’s toll on our bodies. But cancer cells don’t play by the same rules; they do not age. Cancer cells can invade our organs and use our resources indefinitely.

If we grow cancer cells in a lab dish with appropriate nutrients, they’ll grow forever. On the other hand, if we do the same thing with normal cells (even with enough nutrients), they’ll eventually stop growing.

How do cancer cells do this?

When cells divide to make new cells, they lose a little bit of DNA each time. This is normal: to ensure you don’t lose anything important, DNA includes some scrap material. Protective ends of your DNA—called telomeres—help prevent damage to the necessary parts of the DNA. In normal cells, these protective ends get shorter with age (after each cell division). Just as tree rings give away the age of a tree, the shortening of telomeres gives away the age of a cell. Eventually, a normal cell can’t divide anymore as its telomeres get too short to protect DNA, and the cell dies.

Every cell produces a protein known as telomerase that repairs the DNA’s protective ends. In a cancer cell’s mutated DNA, more telomerase is produced than usual. This allows cancer cells to indefinitely protect their DNA ends and avoid the aging process.

Immune-System Evasion: Hiding in Plain Sight

Part of the immune system’s job is to look for any new cancers or precancerous cells and destroy them. This is happening all the time in our bodies.

In the human body, the immune system acts like the police. In fact, the immune system is always on patrol looking for cancer. But cancer cells have ways to keep the immune system from recognizing them. By avoiding the immune system, the cancer can keep on growing.

Cancer cells avoid the immune system by throwing up smoke screens. These cells can also get part of the immune system to help the cancer grow!

How does it do this? The cancer tricks another type of immune cell into destroying the immune cell that was going to destroy the cancer. This is kind of like when internal affairs arrests a good cop, preventing the cop from arresting the criminal (cancer).

Biology: The Big Picture

To summarize, cancer cells are just reflections of our normal cells. Information in cancer cells is moved from the nucleus (DNA) to other parts of the cell. Abnormal cell “thinking” leads to strange instructions being sent throughout the cell. A cancer cell’s only concern is getting enough oxygen and sugar to go on to its next cell division. Cancer cells may move into other areas of the body and take over—or metastasize—to get the necessary nutrients. Cancer can evade the immune system and overcome the aging process.

Now that you understand how cancer cells behave, we can use that information to help identify cancer. We’ll dive into the diagnosis of cancer in the next chapter.