Yes. Yes, I did. But before we get right into that, we need to talk about cell size. Cells are small. For context, a single human hair can be anywhere from 3 to 10 cells wide. So, at first glance, calling a cancer cell “giant” can be a bit confusing. But relative to the size of a normal cancer cell, there are indeed giant cancer cells. A cell’s size is a deeply complicated topic. There are two enormous factors a cell has to consider before it divides: what it absolutely needs to house and how much it costs to make a new cell. When cells divide, every tiny thing in a cell requires effort. They need energy and materials to build, but they also take energy and effort to maintain.

So, when a cell divides, there’s a lot to consider. It has to balance the resources to make and maintain a new cell, while keeping in mind that it needs to be large enough to house all its internal contents. In particular, the biggest component that a cell needs to fit is the nucleus, the compartment DNA is stored in. So, a normal cell is only as big as it needs to be, which makes polyploid giant cancer cells even more curious.

The name “polyploid giant cancer cell” is a really complicated title, so let’s break it up. The prefix “poly” means “many” or “multiple”. “Ploidy” refers to the amount of DNA. Specifically, it refers to an entire set of chromosomes. So, “polyploid” simply means “multiple full sets of chromosomes”. Together, a polyploid giant cancer cell is just a really big cell with extra DNA. This name is actually a good descriptor, because they’re typically several times larger than regular cells and have enormous nuclei, full of DNA.

Getting multiple sets of DNA is an abnormal phenomenon for cells. Just like how they regulate their size, cells put in a lot of effort to regulate their contents. It’s even more important when you’re talking about DNA. Because of the role DNA plays in maintaining and controlling a cell, it’s extremely important to make sure you have the right amount.

A cell with too much DNA can quickly spiral out of control, and that can be a problem.

Because of their awkward set of rules, polyploid giant cancer cells behave completely differently than other cells, including other cancer cells. They grow differently, they move differently, they divide differently, and this is where things become problematic. See, much of our prior research and knowledge of cancer comes from regular cancer cells. That means all of our diagnostic tools and treatments are based on that prior knowledge. As a result, we have profound knowledge and incredible treatments to tackle these cancer cells, but they’re not built to handle different cells.

For example, many of our chemotherapies, the chemicals we use to treat cancer, kill cancer cells by impairing some aspect of cell division. Because of how crucial this process is, it usually leads to the death of cancer cells. But thanks to their abnormal rules, polyploid giant cancer cells replicate differently than normal cells. This means that polyploid giant cancer cells are resistant to many chemotherapies and can survive environments that most cannot.

They’re also capable of lengthy dormant periods. When they’re stressed, like if they’re exposed to chemotherapy, polyploid cells can become dormant. Although they’re not moving around or dividing, dormant cells are still dangerous. They continuously emit signals to other cancer cells that promote division and metastasis. They basically hide and continue to instigate and promote other cancer cells. Because of that, these cells are major drivers of treatment resistance, relapse and recurrence in several types of cancer.

Cancer is already an incredible challenge, and no one wants to have to deal with giant, hard-to-kill cancer cells on top of that. Unfortunately, sometimes we don’t have a choice. Both the size and amount of DNA are tightly controlled, even in cancer. Being too large or having extra sets of chromosomes can be hard to manage, and often leads to cell death. For one reason or another, polyploid giant cancer cells are the exception. Somehow surviving the logistical issues that come with more DNA, polyploid giant cancer cells can be up to 20 times larger than a normal cell. Enormous cells, enormous nuclei, enormous problems. Because of their abnormal set of rules, they behave drastically differently than normal cancer cells. This can lead to treatment resistance, relapse, and more aggression in cancer. Their importance in cancer is also a relatively recent discovery. So, now that we know how important they are, we can start the massive undertaking that is understanding how they work. The more that we know about these cells, the more treatments we can develop and try, and the better we can target them.

I hope you learned a little something this week, but next week we’re going to talk about an interesting new way to subdue cancer: the power of sound.

See you next week!

If you missed last week’s letter, you can read “Cellular Saboteurs” to learn a little more about what oncogenes are and how they work.