About 90% of cancer patients that lose their lives to the disease do so because their malignancy has spread to other parts of the body. For example, breast cancer often spreads to the bones and melanoma cells end up in the lungs. This deadly process is known as metastasis. Metastasis was identified as a Hallmark of Cancer early on in our journey to understand the disease – which means that it is a defining trait of what makes cancer such a deadly and complex issue.
The process of metastasis is defined by a series of consecutive steps which take place one after the other. This is known as the metastatic cascade. Each step in the metastatic cascade requires the successful completion of the previous one. First of ll, cancer cells need to acquire the ability to move and begin invading in the tissue immediately neighboring the original tumor. Secondly, they need to enter blood or lymph vessels in a process known as intravasation. The flow of blood or lymph will transport cancer cells all over the body, allowing them access to very distant organs. Subsequently, they need to exit the vessels in a secondary location (such as the bone for breast cancer cells), in a process known as extravasation. Lastly, they need to start multiplying again in order to form a secondary tumor, or metastasis.
When looking at this diabolical chain of events, we are tempted to assume that cancer cells are voluntarily going though these steps in order to spread. In fact, reality is much more chilling than fiction. There are hundreds of thousands of cancer cells in a single tumor, each one of which has the possibility to accumulate more and more DNA mutations, which allow it to perform new operations. This is because cells in tumors have lost their ability to keep mutations under control, a process know as genomic instability. Cells that have the ability to perform each of these steps progress through the metastatic cascade, while cells that don’t simply stop along the way. There are thousands of cells, for instance, that might acquire the ability to move but not to enter the bloodstream. Their mission to spread throughout the body is therefore a kamikaze-style attempt, where those that don’t make it simply stall and, eventually, die. In a way, cancer is evolving within the body to make it through the metastatic cascade. The “fittest” cells carry on and form metastasis, while those that don’t make it are left behind. In fact, cancer can be looked at as simply the evolutionary process taking place self-destructively within the body.
Each one of the steps of the metastatic cascade is a potential target for new drugs designed to stop metastasis. This is why each one of them is the subject of intense scientific research throughout the world. In this post series, I will go through every step of the metastatic cascade looking at its weak spots and how we can target it using modern drug design. For a full list o