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Advances in treatment of metastatic cancer

Author: Mia James

Historically, metastatic cancers have been notoriously difficult to treat. Advances in treatment, however, are changing the outlook for patients with these diagnoses, as new therapies are able to control cancer spread and even, in some cases, kill cancer cells.

When cancer is metastatic

In short a cancer is diagnosed as “metastatic” when it spreads from the place in the body where it started to other parts of the body. As Glen J. Weiss, MD, Director of Clinical Research and Medical Oncologist at Cancer Treatment Centers of America (CTCA) in Goodyear, Arizona, explains, to understand metastatic cancer it helps to first know how and where the original cancer forms: “The development of cancer involves a sequence of events where cells divide and take on abnormalities. When this division becomes out of control, a tumor results.”

Once a tumor has developed, Dr. Weiss says, it can become metastatic if more abnormalities develop; these include “the ability of cancerous cells to get into the blood and the lymphatic system and travel to and bind to a new location, where they take residence and grow.”

The challenge of treatment

Understandably, metastatic cancers are challenging to treat because they often spread to more than one site, requiring a more complex treatment approach compared with cancer in a single location. The nature of the abnormalities of metastatic cells—their ability to divide and spread—makes therapy even more complicated, as it becomes hard to stay ahead of growth.

“Once cancer cells have spread,” says Dr. Weiss, “it becomes difficult to remove all cancer with surgery or radiation.” He explains that the next step in treatment is to try to target and kill cancer cells throughout the body with systemic chemotherapy—the use of drugs that travel through the blood to cells all over the body. Systemic chemotherapy is primarily given intravenously (through a needle or tube inserted into a vein) or by mouth in pill form.

It can be especially difficult to treat metastatic cancer, explains Dr. Weiss, because cells that are able to spread to different organs can adapt quickly and become resistant to treatment. So it is often possible for a portion of cells within a tumor to survive anticancer therapy. “For example,” says Dr. Weiss, “a one-inch tumor contains billions of cells, and each round of chemotherapy doesn’t kill 100 percent of those cells.” If about 90 percent of cells are killed, 10 percent remain alive and viable and can divide and multiply. “It’s hard to keep up,” he says. A goal of treatment is that the body’s immune cells will begin to help out by developing the ability to identify cancer cells as foreign and then attack and eliminate them.

Meeting the treatment challenge

Despite the difficulties in treating metastatic cancer, there are currently significant advances available to patients and even more improvements on the horizon. Dr. Weiss explains that, in particular, there has been recent progress in the treatment of metastatic lung cancer—specifically, with drugs that target the epidermal growth factor receptor (EGFR) pathway. Known as “EGFR inhibitors,” these therapies work by blocking the activity of EGFR, a protein receptor that is found on the surface of some normal cells as well as some cancer cells and is involved in cell growth. High activity of EGFR in cancer cells causes them to grow and divide, so drugs that block EGFR signaling may help control the growth and the spread of cancer.

“By targeting alterations that cancer cells may acquire in EGFR, EGFR inhibitors can stabilize or shrink a tumor and control additional spread for a long period,” says Dr. Weiss. Tarceva® (erlotinib), he explains, is an example of an EGFR inhibitor approved by the U.S. Food and Drug Administration (FDA) that is currently used in the treatment of non–small cell lung cancer. (Tarceva is also approved for the treatment of pancreatic cancer.)

More advances on the horizon

Future progress in treating metastatic cancer, explains Dr. Weiss, will likely involve therapies that improve the immune system’s response to metastatic cancer cells—drugs known as “immunotherapies.” There are drugs currently in clinical trials (the research process required for FDA approval) that, he says, “stimulate the immune system to identify and target cancer cells.”

For example, a drug called Yervoy® (ipilimumab) has been FDA approved for use in metastatic melanoma. Yervoy is an antibody therapy (a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells) that targets and boosts the activity of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a protein receptor found on T-cells, which are part of the immune system. By targeting CTLA-4, Yervoy can help the body control the growth and the spread of melanoma.

In the treatment of metastatic breast cancer, Dr. Weiss says that emerging therapies combine antibodies with chemotherapy by using the human epidermal growth factor receptor 2 (HER2) on a cancer cell as the target for the antibody. “The antibody binds to HER2, and the chemotherapy agent destroys the cancer cells,” he explains. This combination, he says, is the progression from advances in recent years in HER2-targeting therapies. “But the targeted therapies [antibodies] alone just bind to HER2 and shut down signaling,” Dr. Weiss says, “whereas targeted therapy combined with chemotherapy more effectively attacks cancer.” In breast cancer, therapies targeted at HER2, however, can work only in those cancers that are HER2-positive, which does not include all breast cancers.

Growing options

Though Dr. Weiss cautions that advances in treatment of metastatic cancer do not mean a cure—“They don’t make all cancer disappear, but they can stabilize a patient for years,” he says—he is certain that options will continue to increase. “There are a variety of possibilities for treatment,” he explains, “such as combinations of traditional chemotherapy with antibodies and immune-stimulating agents and targeted therapy.” And doctors will likely be able to use targeted therapy more effectively, he adds, thanks to advances in imaging techniques (such as scans) that help them choose appropriate treatment more effectively.

Each individual advance in the treatment of metastatic cancer represents greater understanding of these types of cancers—how they grow and spread and how we can control or stop them. With that in mind, there is real cause to say that the outlook for treating metastatic diseases is increasingly positive.

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