Why glioblastoma tumors like John McCain's are so aggressive

U.S. Senator John McCain (R-AZ) attends the Senate Armed Services Committee hearing on worldwide threats on Capitol Hill in Washington, U.S., May 23, 2017. Photo by Yuri Gripas/REUTERS

Sen. John McCain, R-Ariz., has been diagnosed with a brain cancer known as a glioblastoma.

The tumor was discovered when McCain's doctors removed a blood clot from above his left eye, which speaks to how the disease may have formed in the first place. (More on that later.)

Though it's is rare overall, with 12,000 new cases expected this year, glioblastoma is the most lethal type of brain cancer. Glioblastoma is dangerous, as many have reported, because of its "aggressiveness." But why? What makes the biology of glioblastoma so unique, and why does that translate to poor outcomes? Here are four reasons.

1. Fast growth

Glioblastomas arise from astrocytes, a type of glial cell. Glial cells, which could account for 80 percent of the brain, are maintenance workers. Some serve as the brain's immune system. Other speed up communications between nerve cells.

Astrocytes are rubbish collectors, cleaning up neurotransmitter chemicals left behind when nerves communicate with each other. They're also the most common glial cell, which may partially explain why glioblastoma is the most common cancer to develop in the brain.

Tumors are grouped by their abnormalities. Glioblastoma gets the highest grade in its family — grade IV — in part because of its high growth rate. These cancers can grow 1.4 percent in a single day. The growth is happening on a microscopic level, but a glioblastoma tumor can double in size within seven weeks (median time). The fastest growing lung cancers, by comparison, have a median doubling time of 14 weeks.

2. Easy spread

Though McCain's doctors said they completely removed the "tissue of concern," the family may still explore chemotherapy and radiation. That's because even small, newly developed glioblastoma tumors can move quickly.

One of the disease's leading traits is a tendency to promote the growth of blood vessels, which supply the tumors with nutrients and oxygen. These cancer-made blood vessels can be poorly built and lead to blood clots.

But blood vessels are the body's superhighways, meaning glioblastoma help engineer their paths toward other parts of the brain. (Fewer than two percent of glioblastomas travel — or metastasize — outside the brain). That's why even if a surgeon catches and removes a glioblastoma tumor, they may want to follow up with chemotherapy or radiation because the tumor may have spread elsewhere.

3. Resistance

You may be wondering: If new blood vessels are the root of these problems, why not use chemotherapeutic drugs to curb their growth? The answer is cancer stem cells. Glioblastoma tumors make their own stem cells, with multiple avenues through which they can cultivate blood vessels — like a farmer that grows more than one crop. Shut down one road to making blood vessels, which doctors have done, and the cancer stem cells will simply switch to another.

Glioblastomas — like all cancers — are spawned by gene mutations, which accumulate naturally over a lifetime. Many chemotherapy treatments target these mutations as a way to identify and kill off cancer cells. But glioblastoma quickly develop ways to reverse the effects of many chemotherapeutic drugs — hence why even when doctors remove a tumor and follow aggressively with chemo, glioblastomas recur 90 percent of the time.

Dr. John Yu, a cancer specialist at Cedar-Sinai Medical Center, has a theory about the origins of McCain's glioblastoma and its connection to his multiple former cases of melanoma, a skin cancer. Long before they became cancerous, these skin cells arose from the embryo's neural crest. This same pool of developing cells splits off to form astrocytes for the brain.

"Presumably it's a cell that had a common origin, whether it was a cell in the skin or a cell in the brain," Yu said. "One would presume a original cell from that area got a mutation — something that was inherited or something that developed over his lifetime" that predisposed him for a cancer.

Watch the NewsHour's William Brangham discuss John McCain's diagnosis, its relationship to the senator's previous cancer and experimental treatments including immunotherapy.

4. Late hitter

While glioblastoma can occur at any age, most cases happen in people 65 and older. Many outlets reported McCain had a 4 percent chance of living at least five years, because he is older than 55. This factoid is misleading, and likely due to people misquoting a figures put out by American Cancer Society for 55 to 64 year olds.

The long-term survival for people over 65 is closer to 1 percent, as indicated by this 2008 study of more than 4,000 people from that age group. To be honest, five-year survival may not be the greatest readout for those over 65, given 99 percent of patients in that study died within three years.

A better metric is likely median survival time — how long patients survive in general — which is approximately four months for glioblastoma patient over 65.

That said, early treatment and early diagnosis can stymie the disease, and odds of survival increase the longer you endure. For instance, Sen. Edward Kennedy of Massachusetts, who was diagnosed with glioblastoma in May 2008 at the age of 76, lived for more than a year after his diagnosis. Experimental therapies for glioblastoma, many of which are in late-stage clinical trials, may extend survival even further in the future.

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