Cancer kills. I know, big surprise. But the average layperson probably have no clue that 90% of cancer deaths are associated with metastasis, or tumor dissemination, and even less people are aware of how metastasis occurs.
At the cellular level metastasis is a very inefficient process; large tumours can shed millions of cells into the vasculature every day, yet very few macroscopic metastases develop – tumor cell successfully relocate very rarely. Yet they still succeed often enough, given months and years, to make up a threat to a person’s health.
So what events does the process known as metastasis comprise? The standard answer goes something like this: Metastasis is the process by which a cancer cell leaves the primary tumor, travels through and proteolytically dissovles surrounding connective tissues, invades the lymphatic system and blood vessels, travels to and attaches at a distant site of the body via the circulatory system, and colonizes a new tumor.
The most common places for the metastases to occur are the adrenals, liver, brain and the bones. There is also a propensity for certain tumors to seed in particular organs. This was first discussed as the “seed and soil” theory by Stephen Paget over a century ago in 1889. For example, prostate cancer usually metastasizes to the bones. Similarly, colon cancer has a tendency to metastasize to the liver. Stomach cancer often metastasizes to the ovary in women, where it forms a Krukenberg tumor. It is difficult for cancer cells to survive outside their region of origin, so in order to metastasize they must find a location with similar characteristics. Breast tumor cells, which gather calcium ions from breast milk, metastasize to bone tissue, where they can gather calcium ions from bone. Malignant melanoma spreads to the brain, presumably because neural tissue and melanocytes arise from the same cell line in the embryo.
Cancer cells may spread to lymph nodes (regional lymph nodes) near the primary tumor. This is called nodal involvement, positive nodes, or regional disease. Localized spread to regional lymph nodes near the primary tumor is not normally counted as metastasis, although this is a sign of worse prognosis.
Whether or not a cancer is local or has spread to other locations affects treatment and survival. If the cancer spreads to other tissues and organs, it may decrease a patient’s likelihood of survival. However, there are some cancers (i.e., leukemia, brain) that can kill without spreading at all.
When cancer has metastasized, it may be treated with radiosurgery, chemotherapy, radiation therapy, biological therapy, hormone therapy, surgery, laser-immunotherapy, or a combination of these. The choice of treatment generally depends on the type of primary cancer, the size and location of the metastasis, the patient’s age and general health, and the types of treatments used previously. Unfortunately, the treatment options currently available are rarely able to cure metastatic cancer, though some tumors, such as testicular cancer, are usually still curable.
Cancer-specific drugs, with Gleevec as the role model, offer hope. By targeting aspects of malignancy, these drugs may retain their efficacy and minimize their brutal side-effects. Some of these drugs may be targeted to specific subgroups of cancer patients, but due to the low numbers of patients for some of these cancer variants, pharmaceutical companies may be disinclined to develop such drugs. Additional hope may be found in uncovering the cellular adhesion factors and other attractants that influence what tissues various cancers primarily migrate to.
Q&A: Metastatic Cancer – from the National Cancer Institute
Cancer Topics – from the National Cancer Institute