By: Annie Hu
The estimated number of new cancer cases and cancer-related deaths for 2020 are staggering. 1.8 million new cancer cases and 606,520 cancer-related deaths are estimated to occur in the U.S alone. These cases consist of many different types of cancer, with the most common being breast, lung, and prostate cancer. While each type of cancer has its own unique features most have one thing in common: the ability to metastasize, or spread to distant body parts after breaking away from the primary tumor to begin wreaking havoc on the rest of the body. This worsens the prognosis of the cancer and is a likely indicator of an advanced stage. For many cancers, the onset of metastasis automatically puts it in stage 4, indicating that the cancer has reached an extremely dangerous stage.
So, how does cancer spread? In order to achieve metastasis, cancer cells must undergo a series of processes and experience favorable conditions for growth at each turn. A group of skin cells living in the liver will need to be able to thrive in such a new and foreign environment. First, the cancer needs to spread to the nearby tissue, by growing into and invading it. For example, in melanoma, a type of skin cancer known for its metastatic potential, the first step of metastasis is a vertical growth phase. In this phase the melanoma tumor begins to invade deeper layers of the skin and spread to nearby tissue.
Next, the tumor needs to invade lymph nodes or blood vessels. Angiogenesis (or the formation of blood vessels) plays a huge role in getting tumor cells around the body. Normally, cancer cells promote angiogenesis and interact with the vasculature at their new site to provide them needed nutrients like oxygen, which help them to continue growing and spreading. The lymphatic system and the bloodstream are the main modes of transportation for metastatic cancer. When the cancer finds a suitable area to plant itself, it stops in the blood vessels and invades the tissue, growing until a tumor forms. Before growing, the tumor sometimes experiences a period of metastatic dormancy where it lies inactive at its new site.
Where the cancer is likely to spread depends on the type of cancer and where the primary tumor was originally located. Because cancer travels through the lymphatic system or bloodstream, it is most often deposited in a nearby organ “downstream” of the source. For this reason, certain cancers may prefer to metastasize to certain areas. An example is metastatic breast cancer, where a common site of metastasis is the underarm. A widely accepted hypothesis on why cancer spreads and lands where it does is the “seed and soil” hypothesis proposed by English surgeon Stephen Paget. This proposes that the tumor, once the cells overcome cell-cell and cell-matrix adhesion within its primary site, releases cells (seeds) in all directions, and only those which land on suitable soil will grow. While this hypothesis is widely accepted, it does not go unchallenged and other hypotheses have been formed regarding metastasis. For example, it has been theorized that metastasis depends purely on mechanical mechanisms like blood flow patterns. However, evidence points to a huge role of both a suitable microenvironment as well as the mechanics and blood flow. There is much to be uncovered about where tumors are likely to spread during metastasis and how best to treat metastatic cancers.
In order to diagnose metastatic cancers, local lymph nodes and tissue around the primary tumor must first be examined, as spread to surrounding tissue increases the risk of metastasis to a distant organ, which is more dangerous. Most cancers metastasize to the liver, lungs, lymph nodes, and bones, so those areas are tested first for the presence of a foreign tumor. In a new environment, tumor cells can be detected by their differing cell traits, which are representative of the organ and area that they originated from. Because the metastatic cancer cells have features of a different body part, doctors can usually tell that they have spread from another part of the body.
Metastatic cancer is an advanced stage and is the cause of many deaths in cancer patients. This is because the more widespread a cancer is, the harder it is to treat. However, new treatments have been developed that attempt to slow the growth and spread of the cancer since metastasized cancer does not yet have a treatment that can completely eliminate it. These new treatments are called systemic therapies, and consist of medications taken orally or injected into the bloodstream that are used to treat metastatic cancer. Systemic therapies may reach cells throughout the body, thus treating more widespread cancers. Some examples of common therapies are chemotherapy and hormone therapy, immunotherapy, radiation therapy, and surgery. In combination with treating the cancer itself, palliative treatments are used to relieve the symptoms and side effects.
It is key to understand how cancer metastasis works so we can develop better treatments and preventative measures. Metastasis is a feature of advanced cancer and is the cause of many patient deaths. A better grasp on this aspect of the disease may help us learn to diagnose and more effectively treat late stage cancer. I hope you enjoyed reading about cancer metastasis, and this important and interesting aspect of advanced cancer.
Citations:
https://www.cancer.gov/types/metastatic-cancer www.cancer.org/cancer/melanoma-skin-cancer/about/what-is-melanoma.html
Images:
No changes were made to the following image, Chemotherapy | A word cloud featuring "Chemotherapy". Would … | Flickr, License: Creative Commons Legal Code
What Did You Learn?
Questions:
1. What does metastasis tell you about the cancer’s development and prognosis? How is it treated?
Metastasis is a big indicator of advanced cancer. Spread to distant organs makes the cancer harder to treat since the tumor is not only contained within its primary site. For most cancers, reaching a stage where tumors are found in distant organs means Stage 4, putting patients in a deadlier prognosis. Metastatic cancer also requires specific treatment to slow the growth and spread. Systemic therapies like chemotherapy, hormone therapy, radiation therapy, immunotherapy, and surgery would likely be applied for this, in conjunction with palliative treatment.
2. What are some theories regarding why cancer spreads to certain locations over others?
Two common theories that have been widely accepted regarding metastatic deposits are the “seed and soil” hypothesis and the “mechanical mechanisms." The seed and soil hypothesis proposes that a tumor that has acquired the ability to overcome adhesion and gain the motility needed for metastasis disperses in all directions, travelling through the body and growing wherever the environment is suitable. The mechanical mechanisms hypothesis proposes that the dissemination of the cells depends solely on mechanisms like blood flow and circulation, which ends up depositing cells to certain target areas. Recent evidence suggests a role of both mechanism and seed-soil compatibility.
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