When Cancer Spreads

Improving Treatments for Metastasis

A cancer diagnosis can be scary. Some cancers can be cured if caught early. Treatments like surgery, radiation, and chemotherapy can destroy many early-stage cancers. But cancer can be difficult to treat when caught later on, after it spreads.

Cancer cells are sneaky and stubborn. They are hard to stop from growing and spreading. Cancer cells can also break away from their original location and settle in other parts of the body.

When this happens, it’s called metastatic cancer, or metastasis. This is sometimes called stage 4 or stage IV cancer. When cancer migrates to other organs, it can disrupt their function and cause life-threatening problems.

Metastatic cancer is serious and hard to treat. In fact, most cancer-related deaths (about 90%) are caused by metastatic cancer and not the original tumor, called the primary tumor.

Researchers have been working to better understand how metastasis occurs so they can find new ways to prevent or treat it. Thanks to medical advances, some people can live for many years with metastatic cancer when it is well-controlled.

Adapting to New Locations

Cancer cells can spread to almost any part of the body. The liver, lung, and bones are the most common places. Different types of cancer tend to spread to certain locations. For instance, pancreatic and colon cancer commonly spread to the liver. Breast cancer and a type of skin cancer called melanoma can spread to the brain.

Metastatic cancer is considered to be the same type of cancer as the original tumor, even though it has moved to a new place.

“It can sometimes be confusing. Breast cancer that spreads to bone is still considered to be breast cancer and not bone cancer,” says Dr. Rosandra Kaplan, a physician and cancer researcher at NIH. “So a patient with cancer may have bone pain or feel a lump somewhere else. But it doesn’t mean there’s a new primary cancer. It’s most often the original cancer. But it has figured out how to escape and grow in a new place.”

Researchers have been scrutinizing how cancer cells do this. Once cells break away from the original tumor, they can squeeze into blood vessels and travel to other sites. At this point, escaping cells are usually destroyed by the body’s The system that protects your body from invading viruses, bacteria, and other microscopic threats. immune system.

But sometimes our own body helps hide or protect the tumor cells. If any cells survive, they can take root in a new location. The cells can form a growing clump that prompts new blood vessels to grow. This blood supply then helps the metastatic tumor to thrive.

Cancer cells have to undergo many changes to survive in a new part of the body. They keep some features of the original tumor cells.

“But we are learning that as cancers become metastatic, they become very different from the primary tumors they started off as,” explains Dr. Karuna Ganesh, a physician scientist at Memorial Sloan Kettering Cancer Center. “Once these cancers spread, they become really hard to treat.”

The treatments used to shrink the original tumor become much less effective in the cancer that spreads. Ganesh and colleagues have been studying the complex changes that occur when cancer cells adapt to new environments. They’ve found that the invading tumor cells can easily turn different genes off and on. This helps them adapt to new places and resist treatment.

“We’ve found that there’s a crosstalk between the tumor cells and the surrounding cells. The cancer cells can reprogram the surrounding cells to support them,” Ganesh says. “By understanding this crosstalk, we can manipulate those interactions to better control the cancer cells.”

Revving Up Defenses

In recent decades, scientists have uncovered new ways to use the body’s own immune system to fight cancer. This is called immunotherapy. One type, called immune checkpoint inhibitors, is now widely used. It can extend the lives of many patients with metastatic cancer.

“Tumor cells are good at hiding from the immune system. They do this by displaying proteins that send the signal: ‘Do not attack me,’” explains Dr. Christine Nadeau, an NIH expert on metastasis. “Immune checkpoint inhibitor drugs block those protein signals.” This “unmasks” the cancer cells so immune cells can destroy them.

Immune checkpoint inhibitors can treat patients who have metastatic melanoma and some types of kidney, lung, head, and neck cancers. Although these drugs can be effective, they don’t work for everyone. And they can have harsh side effects. Researchers are developing artificial intelligence tools to help doctors identify who will most likely benefit from these drugs. That way, patients who won’t be helped can receive different treatments.

Another type of immunotherapy is called cell-based therapy. It essentially uses a person’s own immune cells as drugs. “Cell therapies involve removing some of the patient’s immune cells and then altering them so they can work even better against their cancer,” Kaplan says. The enhanced immune cells can be grown in large batches and injected back into the patient’s bloodstream.

One type of cell therapy, called CAR T-cell therapy, has been used for years to treat some blood cancers, like leukemia. In early 2024, the U.S. Food and Drug Administration approved the first cell-based therapy for treating a solid tumor. It’s used to treat metastatic melanoma. Recent clinical trials at NIH have used other types of cell therapy to treat people who have metastatic cancer of the colon or breast.

“Cell therapy may become a real game-changer for many patients with metastatic cancer,” Kaplan says. She is now leading a first-in-human clinical trial to see if another type of immune cell therapy, called GEMys, can keep cancer from spreading.

Coping With Metastatic Cancer

“A diagnosis of metastatic cancer can be overwhelming,” Nadeau says. “But treatment options continue to improve. There are reasons to be hopeful.”

The goal of treating metastatic cancer is usually to stop or control its growth to extend the person’s lifespan. Other treatments are designed to relieve symptoms and improve quality of life. This type of treatment is called palliative care. It can be given at any point during cancer treatment. Learn more about palliative care.

“Joining advocacy or support groups for your particular cancer can also help,” Nadeau adds. “These groups include people who have been through similar treatments. They understand the challenges.”

Learn more about coping with cancer.