Monthly Archives: August 2016

Chasing Down Metastatic Cancer

Mike Mets Blog PostWhat is metastatic cancer?

Cancer has many nasty features that make it one of the most difficult and complicated diseases to treat and cure.  It doesn’t sit still- it is constantly growing, changing and moving.  In simple terms, metastatic disease is cancer that has spread from the original tumour to another location in the body and set up shop.  Metastases (commonly called “mets”) may not go very far and just form another tumour within the initial affected tissue, or they can travel great distances to different organs.  Mets can be discovered at the same time as original diagnosis, or can remain undetected for months, or even years.  If cancer reoccurs in a patient previously treated, it is most likely a met.

How do metastases spread?

Although most cells are normally immobile, cancer cells can “turn on” a set of genes that exist in all cells, which allows them to move around and travel to new locations in the body.  This set of genes exists because some normal cells have to be able to migrate when needed. For example, if you were to cut yourself, skin cells must replicate and travel to the cut site to heal the wound.  Immune cells also move freely around the body looking to respond to danger, such as bacteria and viruses.  Metastases are an example of a type of cell, specifically cancer cells, hijacking normal cellular processes for their own benefit.

When these migrating cells move away from the initial tumour they may not travel too far to form a second tumour near the original. By definition, though, this is enough to be called a metastatic tumor.  However, what this really indicates is that these cancer cells have acquired the ability to spread, and it is this behaviour that signals the possibility that they have spread to more distant locations in the body.  Metastasizing cells travel in the blood stream or lymphatic system (a series of vessels that immune cells use to travel across the body), and use these systems as highways to access any location in the body.  Some types of cancer prefer to travel to particular locations: breast cancer often relies on calcium for its growth, so it often spreads to the bones, which are full of calcium ions.  Also, it is common for skin cancers to metastasize to the brain since skin and brain cells have a common origin during development.  We can think of cancer cells as the “seed”, but they also need to be in the right “soil” for a met to take root. This highlights an important point- since mets are so dependent on particular signals found in their new location, this is weakness that can be exploited.

So as you can see, it is no small feat for cancer cells to metastasize!  Cancer cells must break away from the original tumour, find their way to either the blood or lymph vessels, travel to another site in the body and survive well enough to start growing in an entirely new environment.  All this while evading the body’s immune system.  Some of these properties are reminiscent of cancer stem cells, as metastasizing cells do not proliferate, can lie dormant for long periods of time, and are capable of creating a new tumour. Scientists want to study and understand exactly how these cells are capable of these tasks to prevent, help detect and treat cancer cells that have metastasized.

How is metastatic cancer treated? How do we study it?

Metastatic cancer is still named after the original, or primary cancer. For example, breast cancer cells that have spread to the lung are called metastatic breast cancer, not lung cancer.  This means that these cancer cells share common features with the original tumour, such as how they look (morphology) as well as genetic and molecular features allowing chemotherapeutics that a patient is taking for the original tumour to also have some effect on the metastasizing cells and slow their growth.  Similar to treating the original tumour, mets are targeted by surgery and radiation to slow their growth and spread, but also present their own challenges.

One major hurdle in studying metastases, is that, by definition, they are only found and diagnosed after they have metastasized, which is often at later stages of the disease.  This makes it difficult to study the processes of how they form; mets start from very small numbers of cells- and in theory even a single cell can give rise to a metastatic tumor.  Finding one cell within trillions of normal cells is nearly impossible.  To get around this problem, some research groups label cancer cells with fluorescent markers before injecting them into mice.  Over time, mice develop cancer, or a tumor, in an initial tissue.  The researchers then wait and watch for some cells to metastasize to different locations in the body.  Since these mets now “glow in the dark”, they literally shine like beacons to researchers, allowing them to be found and studied at a genetic level.  One of the most powerful aspects of these sorts of studies is that it is very tightly controlled. The exact properties of the starting cells are known, allowing researchers to more easily pinpoint the precise genetic changes that took place for metastasis to occur!

What is interesting, is that when you compare a patient’s mets at a genetic level, it doesn’t matter if they started in the breast, prostate or lung: they are actually more similar to each other, than to the cancer cells found at their tissue of origin.  Although this can complicate therapy since these metastatic cells have evolved or adapted, having this  core similarity is encouraging from a therapeutic perspective based on the idea that drugs can be developed to target all of a patient’s mets, no matter if they’re in bone or lung.

Some of the latest therapies designed to target metastasizing cells are a branch of immunotherapy.  These strategies “rewire” or enhance a patient’s own immune system to target and destroy cancer cells.  One advantage unique to immunotherapy is that immune cells can move around the entire body and chase down metastasizing cells, no matter where they are located

Finally, let’s remember that cancer metastasis is a complicated process with many steps.  This is good news!  Researchers can devise therapies targeting any one of these steps.  It is likely that treatments will one day include destroying the “seed” or cancer cells, and tainting the “soil” or environment in order to contain and prevent mets.  Although metastatic cancer poses a significant challenge to the research community and patients alike, it is just another roadblock, or hurdle, to overcome.  Each and every day, we get one step closer.

This article was written by Mike Pryszlak. Mike is currently completing the third year of his PhD at the University of Toronto. He studies how normal stem cell genes are changed in cancer stem cells. To learn more about Mike and his research check out our members page.