Cancer

Let’s start this blog by talking about a complex topic: cancer. I’ve been studying cancer for a couple of years now (I have a degree in cancer biology, that makes me an expert, right?), so I know quite a bit about it. Of course, it’s a difficult topic to talk about because there’s so much to talk about. There’s a lot of details about cancer that are difficult to explain in a blog post, but I’m going to give it my best shot by giving a general overview of what it is.

I would be surprised if anyone reading this has had no personal experience with cancer. This could be through a family member, a friend, a friend-of-a-friend, even yourself. There’s really no need to answer the first question that pops into my mind, which is what is cancer? I’m sure we all know cancer is a disease that essentially attacks and weakens the body. The more important question here is why do we get cancer?

The human body is, for the most part, exceptional at taking care of itself. There are a million tiny reactions and interactions and processes that occur in your body every minute, and these go right about 99% of the time. Knowing a lot of the minute details about how we function, it’s amazing that we can work at all.

Before I get too reverent about the human body and how it functions, let’s move on to the nitty gritty. Cancer occurs when a multitude of these tiny processes go wrong. Let me be clear, especially because this may help you understand exactly how complicated cancer is: cancer is not one problem, it’s a multitude of problems that gradually add up. For example, perhaps you have you heard of the BRCA mutation, which has gained some media attention over the past few years. It is a gene that’s often used as a genetic marker for breast cancer risk in women. I think it’s important to clarify that this mutation alone will not cause cancer, it’s just one piece of a bigger puzzle, and you need many pieces before you can see the picture (in this case, developing cancer). Having this mutation increases cancer risk because it is simply one step closer to getting breast cancer.

(Side note: if you have had the genetic test done and you do have a mutation in the BRCA gene, it is not a guarantee that you will get cancer so please don’t panic)

Let me provide a really simplified example of what this can look like. We have a woman named Joanna (I apologize if your name is Joanna, it was the first name that popped in to my head, I’m not saying any of these things apply to you). Let’s say Joanna was born into a family with an extensive history of cancer, her father smokes, and she hardly wears sunscreen. These are all factors that play into Joanna’s cancer risk.

On the other hand, we have a guy named Tom. Tom was born into an extremely healthy family with a small history of illness, no one around him smokes, he exercises regularly and eats well, works in the city in an office job, and drinks socially on the weekends. These are all factors that play into Tom’s cancer risk.

These examples are intentionally super different from each other. However, both people develop cancer at some point in their lives. Perhaps Joanna contracts metastatic (meaning an aggressive form of cancer) breast cancer in her 40s, while Tom develops testicular cancer in his 70s. Why is this?

First, cancer is, at its core, an age-related disease. This means as you get older, your chance of developing cancer increases dramatically. This probably isn’t that surprising, as overall health and wellness begins to decline at a certain age anyway. But the main reason cancer is age-related comes from all those tiny reactions that occur in your body all day, every day. You are basically a machine, and like any machine, general wear and tear occurs naturally. You get worn down, things stop working as well, and mistakes get overlooked.

Second (and possibly more important), cancer is a loss of control. This goes hand-in-hand with the idea that it’s an age-related disease. Tumors, which are the physical manifestation of cancer (basically a big pile of cells growing where they shouldn’t), are the prime example of this loss of control. Cells are constantly growing and dividing, yet this is strictly regulated in what’s called the cell cycle. The cell cycle dictates whether a cell is fit for replication (which means replicating all the DNA in a cell) and division (which is when a cell splits in two), or if it should be prevented from continuing in the cycle. As a fun side note, cells that are prevented from continuing are either marked for destruction (a process called apoptosis, which is a fun word to know) or simply be stuck in a permanent state of no growth (called senescence, which is a way to keep the cell while preventing it from possibly becoming cancerous). Cancer occurs when a “bad” cell (we’ll talk about what makes it bad in a minute) escapes this regulation and produces more “bad” cells. This escape quickly gets out of control, which results in formation of a tumor.

There is a famous review article in the cancer research world called “The Hallmarks of Cancer.” For those who are really interested, I’ll put a link to the pdf below (along with an updated review called “The Hallmarks of Cancer: The Next Generation” which was published about 10 years later). These review articles laid out the common molecular events that lead to the development of cancer. It started with six common “hallmarks,” but has now been increased to ten. Out of the original six, four had to do with this escape from cell cycle control.

What constitutes a “bad” cell? Unfortunately, I don’t know everything that could produce a “bad” cell, because there are so many possibilities. But I’m going to quickly go through two major players.

 

A mutation in an important gene.

Of course, the logical question here is what makes a certain gene important? There are two classifications of important genes that, when mutated, can lead to cancer:

1. Tumor suppressor – a tumor suppressor gene is exactly what it sounds like. It is a gene that works to prevent tumor growth and this loss of growth control. The most famous tumor suppressor is a gene called TP53, which encodes for a protein called p53. When these tumor suppressor genes are mutated, they can no longer protect cells the way they are meant to. These types of mutations are called inactivating.
2. Oncogene – oncogenes are the opposite of tumor suppressors, in that their mutations are called activating.  This is because oncogenic mutations lead to an increase in factors that contribute to loss of cell cycle control.

Tumor suppressors lose function of cancer protectors, while oncogenes gain function of cancer enhancers. For tumors to grow, there needs to be both inactivating and activating mutations. Accumulation of these mutations is what eventually leads to tumor formation. Not to use this point too much, but these mutations accumulate more as you get older, which contributes to cancer risk increasing with age.

 

DNA damage.

I’m sure most of us are familiar with the idea of DNA. It’s the code of human life, it dictates most events in the body. All cells contain a complete copy of your DNA (so you have millions of copies of the same code), and uses it accordingly based on where the cell is located in the body. When a cell divides, it needs to make an exact copy of all the DNA. To get some perspective on how massive this task is, if you stretched the DNA from one cell, it would be approximately six feet long (according to the National Institute of General Medical Sciences). Most cells replicate this amount of information multiple times a day.

However, this system isn’t perfect. Mistakes do happen, and they happen quite often. In normal cells, these imperfections can be detected and repaired, or the cell is marked for elimination (review: called apoptosis). A lot of the genes involved in this pathway are tumor suppressor genes (TP53 again being one of the prominent genes involved). As you get older and accumulate mutations in these tumor suppressors, the body gets worse at both detecting mistakes in DNA replication, and repairing them. When this happens, imperfect cells are allowed to pass their “bad” DNA on to other cells, which then pass the mistakes on to more cells, and so on and so forth, until you have a big pile of cells that all have similar mistakes in their DNA that can’t be repaired and BOOM! Suddenly you have a tumor. Well, maybe not so suddenly as this process takes years.

I would assume another question you might have is what causes this DNA damage? To be honest, the factors that can induce this damage are so vast, it’s better left for a separate blog post.

However, let’s think back quickly to our pals Joanna and Tom. A lot of things in Joanna’s life increase her risk of cancer, some quite drastically. Smoking, for example, is a huge factor in cancer risk. It is the number one (ENTIRELY PREVENTABLE I might add) cause of lung cancer, because smoking pumps your lungs full of chemicals that can easily damage DNA. Her family’s history of cancer and a lack of sunscreen use (UV rays from the sun can cause DNA damage in skin cells) increase her cancer risk even more.

Tom, on the other hand, leads a pretty healthy life. In terms of cancer risk, he does everything right. Healthy lifestyle, no family history, etc. But like Joanna, he still develops cancer. The difference here is that his cancer comes much later in life. Tom manages to keep those cancer-causing factors to a minimum, thereby prolonging their additive effects. Luckily for them, their cancers have many successful treatment options, so they get to outlive their cancer.

 

Conclusion.

This is a very, very broad overview of cancer. It’s such a complex disease, even entire books can’t cover everything about it (though there’s one that tries, and does an outstanding job, I’ll include it below with some other resources). I do want to end though, with one final thought, which often is my answer when people ask why hasn’t cancer been cured yet?

People worry that we’ve spent over a hundred years and billions of dollars studying this disease, and have gotten nowhere because we don’t have a full cure. Let me reassure you, we have certainly gotten somewhere. We have come so far in understanding the underlying mechanisms of cancer, which has led us to new and more effective treatment options, which has led to a drastic increase in cancer survival rates. Yes, we have yet to find a complete cure for cancer (for all you conspiracy theorists out there, big pharma is NOT hiding a cure for cancer), but we are getting really good at detecting cancer earlier and getting patients into remission and keeping them in remission, often for their whole lives.

Lastly, if you or someone you know has cancer, there is so much hope. It is heartbreaking news to receive, but there are so many resources available, and every day these resources are getting better and better.

 

Resources:

Disclaimer – the majority of this post comes directly from my mind and what I’ve learned over my studies. Any additional facts/information I have gotten from the resources below. Feel free to fact-check me or read additional information for your own personal gain!

Scientific Literature (you made need special access for these)

• “The Hallmarks of Cancer”, Hanahan and Weinberg, 2000 – cancer review article
• “Hallmarks of Cancer: The Next Generation”, Hanahan and Weinberg, 2011 – cancer review article
• “Age-Specific Prevalence of Epstein–Barr Virus….”, Balfour et al, 2013 – prevalence of EBV in school children

Books

• The Emperor of All Maladies, Siddhartha Mukherjee – one of the best books I’ve ever read, all about the history of cancer

Helpful Websites

• https://publications.nigms.nih.gov/insidelifescience/genetics-numbers.html – factoids about DNA