Cancer: when orderly processes go awry

Day 10 by Jay Reed,

Let’s say you are a customs and immigration officer at an international airport.

You have two important tasks to perform. First, you need to ensure an efficient flow of traffic through your station. This means making sure the people get through in a timely manner.

But equally important, you need to prevent bad guys from getting through without a proper screening. This is no easy task, and it takes several moving pieces. You’re a low-level officer, but you’re pretty well-trained at identifying shadiness when you see it. And there’s a system in place to make sure things go smoothly

In some cases, you can make the call yourself and halt the shady character. In other cases, you need to consult your superiors and let them make the call. In even other cases, your supervisors have to consult their supervisor to make the call. Better safe than sorry, no?

Now, there are some checks to your power. Let’s say anytime you stop a person, they can ask for an attorney. The attorney advocates for the person to get through as fast as possible. They don’t care about all your rules - they just want to get their client out of the door. Once you decide the passenger is OK, they immediately go through.

Now what happens when things fall through?

You aren’t perfect. Your bosses aren’t perfect. Not to mention the lawyers are sometimes very good at confusing you. There are some things that could go wrong:

(A) You mess up

You’re tired, you’re hungry, you’re sick, or in some other way not at the top of your game. You really ought to have stopped that shady person, but that would have required a lot of paperwork. All you want to do is pop some nasal decongestants and head home. Unfortunately for you, you’ve just let in a bad guy who can cause harm.

(B) Your boss or boss’s boss mess up

You’re really sharp today, and you’ve been identifying shady people all day. But your boss has inextricably let them go through against your better judgement. They’ve let in a bad guy, and everybody suffers for it.

(C) The lawyers are especially good today

Both you and your bosses are working well but, man, those lawyers are really, really sharp today. They are making all these arguments that you’ve never heard before and don’t really understand. If you don’t abide by their demands, you and your boss are afraid you’ll get into trouble. You succumb and let the shady person through.

The story of cancer

The cast described in this story are representative of the players involved in cancer.

Cells are the building blocks of all of us. Cells come in different shapes, sizes, and functions. They work together to perform various functions important for sustaining life. However, they don’t last forever.

When they are past their prime, they clone themselves through an ordered process called the Cell Cycle. This is a highly regulated process with major checkpoints and layers of control -- sorta like that customs/immigration line we’ve been talking about.

Those passengers trying to get through your checkpoint - they are like cells going through the cell cycle. Like the passengers, cells need to go through several checkpoints that ensure they are fit and proper for replication.Cancerous cells are not fit and proper - for a variety of reasons (radiation, toxins, randomness) they have accumulated mutations in their DNA that cause them to grow and proliferate uncontrollably. They ought to be stopped and normally they are.

That’s where you and your boss come in - you’re the special proteins responsible for regulating the progression of cells through these checkpoints. We call you guys tumor suppressors since well, when left to your own devices, you suppress the cell cycle. If you guys become defective, you could let these potentially cancerous cells progress through the cell cycle -- when they really ought to have been stopped, corrected, or destroyed. And because these cells weren’t stopped, they can go on to cause cancer.

And those pesky attorneys bugging you can make things worse -- they are akin to the proteins responsible for making sure the cells get through their checkpoints with ease. These proteins are called proto-oncogenes. Normally, they are good because they ensure a regulated flow - our body needs to be efficient to thrive. For this reason, they promote the cell cycle when left to their own devices. However, if these proteins (then called oncogenes) gain too much power, they can get a little haphazard and cocky and let cancerous cells overcome tumor suppressor obstacles by inhibiting the normal suppressor function. Again, this can lead to cancer.

Uncertain fate, uncertain future

What makes cancer so unpredictable is that so many different combinations of problems can lead to the same outcome -- unregulated progression through the cell cycle of a malicious cell. This cell, through its various DNA mutations, then has the potential to grow and divide at will.

Fortunately for humans, our machinery typically identifies these mutations and makes sure those cells don’t get any further. We can also survive a few sporadic episodes here and there because of other mechanisms in place.

To actually get cancer, the cell itself usually has to have many mutations. Not only that, multiple different officers/bosses need to underperform and/or multiple attorneys need to overperform. Because normally the system does a pretty good job of identifying those problematic mutations.

But with any process that happens a whole lot, the more you go through the motions, the more likely things are to go wrong. That’s why cancer tends to affect rapidly replicating cells (i.e. colon cancer, liver cancer, breast cancer) and not affect cells that barely replicate (i.e. you don’t often hear about heart cancer because heart cells don’t replicate much).

As the process’s machinery gets old and rusty, the more likely things are to go wrong. DNA mutations are more common because of rusty machinery, and the tumor suppressors could also lose steam or function. That’s why cancer is thought to be a disease of the aging.

Cancer is pretty complicated collection of many different concepts in biology, but it’s generally described as the an unopposed, uncontrollable, and malignant replication of one or more cells in our body. Our body typically sniffs these problems out and doesn’t let these cells divide. But sometimes this can go off and it can lead to cancer. Good thing we have star agents like yourself to screen the bad guys out....

Vinayak Venkataraman is a rising second-year medical student at Duke University School of Medicine. He graduated from Princeton in 2011 with a degree in Electrical Engineering and certificate in Bioengineering. After graduating, he worked with Dr. Ray Dorsey at Johns Hopkins, researching the feasibility and value of using web-based videoconferencing (i.e. telemedicine) to expand access to care for patients with Parkinson disease. Outside of medicine, Vinayak is the author of an awesome novella and loves Indian cooking, tennis, and coffee.

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