Warming up to hyperthermia: heat therapy could improve existing cancer treatments

Science News,  Oct 14, 2006  by Christen Brownlee

• E-mail
• Print
• Link

In March 1999, Jason Foster was unpleasantly surprised by a BB-size lump that he found in one of his testicles. He ignored it for a week, hoping that it would go away. But instead, the lump swelled to the size of a pea. "I had alarm bells going off in my brain," recalls Foster. A trip to the urologist confirmed his fears--Foster had testicular cancer. The news set him on a grueling, 4-month path of surgery and multiple chemotherapy drugs. Foster lost his hair, spent hours throwing up, and was exhausted. To stay upbeat, he tried to keep the disease in perspective.

"I knew I'd have a positive outcome on the other side," says the 36-year-old media-relations director at San Diego State University. "I still think of myself as having had minor league cancer. Those with breast, lung, and other cancers, they go through treatment, and there's no guarantee that they'll make it."

Foster's take is correct: Among cancers, testicular cancer is unusually curable. Even when the cancer has migrated elsewhere in the body by the time of diagnosis, about 72 percent of men are still alive 5 years later. In contrast, the 5-year survival rate for breast cancer is about 26 percent after it spreads.

Researchers have puzzled for years over what they call the "Lance Armstrong effect," named after the world's most famous bicycle racer and testicular cancer survivor. Some scientists propose that a single factor--heat--could be responsible for this cancer's relatively easy cure. Testicular cells normally stay a couple of degrees cooler than other cells in the body. The cooler cells can't survive normal body temperatures, and researchers speculate that they retain this vulnerability even when they become cancerous and spread to other parts of the body.

"The hypothesis is that that slight temperature change is enough to put them on the cliff's edge, so just a slight nudge from chemotherapy or radiation makes them die when they wouldn't die otherwise," says Theodore DeWeese, a radiation oncologist at Johns Hopkins University.

Researchers have applied this principle to other types of cancers. By simply ratcheting up a tumor's temperature a few degrees--similar to the tiny temperature difference between the testes and the rest of a man's body--scientists are boosting the power of radiation, chemotherapy, and cancer vaccines. Armed with a better understanding of how heat amplifies those treatments' effects and with new tools to heat tumors, researchers may someday give every cancer patient the bright prognosis of Foster, Armstrong, and other testicular cancer survivors.

HEATING UP The idea of prescribing heat, or hyperthermia, to cure whatever ails you spans hundreds of years, says cancer researcher Donald Coffey of Johns Hopkins University in Baltimore. "There's no culture in the world that doesn't believe that hot springs and baths are good for you," he adds.

In the late 1800s, a New York bone surgeon named William Coley discovered that cancer patients who came down with infections--and fevers as a consequence--sometimes experienced remissions. He achieved similar results by injecting patients with bits of bacterial cell walls, which prompted fevers without infections' other dangers.

Almost a century later, in the 1970s and 1980s, researchers renewed attempts to kill tumors by heating them with microwaves, ultrasound, or other methods. "We had our sights set on killing tumor cells directly to make hyperthermia effective," says radiation biologist Mark Dewhirst of Duke University Medical Center in Durham, N.C.

As researchers developed more-accurate ways to measure internal temperature, they made a surprising discovery. "We found out that temperatures too low to kill cells were quite effective in sensitizing tumors" to other treatments, Dewhirst says. Temperatures that were a mere 2[degrees]C to 9[degrees]C warmer than body temperature could make a difference for cancer treatments.

It's not clear how higher temperatures sensitize cells. One possibility is that heating improves a tumor's blood flow, delivering more chemotherapy drugs to cancer cells. Better blood flow also delivers more oxygen, a pivotal ingredient in making radiation treatments effective.

Heat also deforms the vast array of proteins necessary for normal cellular functions, explains radiologist Joseph Roti Roti of Washington University in St. Louis. Some proteins bend when warmed, exposing molecular segments that stick to other proteins. "This is like putting rust in the machinery," he says.

Hotter temperatures also seem to have a dramatic effect on the immune system, says immunologist Elizabeth Repasky of Roswell Park Cancer Institute in Buffalo, N.Y. Studies in her lab and elsewhere' have shown that fever-range temperatures increase the infection-fighting ferocity of immune components such as dendritic cells and macrophages. Such an increase in immune power could also potentially fight off tumors, Repasky says.