By Alexandra Goho

Dousing the Flames of Cancer

Treating chronic inflammation may be crucial to preventing the disease

By Alexandra Goho

So he has turned his attention to another molecule, called interleukin-6. The main risk factor for developing liver cancer is chronic liver damage caused by infection with the hepatitis B or C viruses. Such liver damage causes macrophages in the organ to release interleukin-6. This inflammatory molecule is regulated by NF-κB and stimulates the proliferation of liver cells, including those that have acquired mutations, in an effort by the body to maintain constant liver mass. Karin and his colleagues have shown that blocking interleukin-6 in mice with liver damage or giving the animals antioxidants dramatically slows the development of liver cancer.

But the biochemical signals sent by macrophages, which are part of the body’s first line of defense against foreign invaders, are only one side of the immune system’s role in inflammation and cancer. The immune system also includes specialized cells—B cells and T cells—that learn to recognize and destroy specific pathogens. In a study published in 2005, Lisa Coussens, a cancer biologist at the University of California, San Francisco, and her colleagues found that B cells, which normally produce antibodies against viruses and bacteria, are the real perpetrators of inflammation-associated cancer.

When Coussens’ group genetically eliminated B cells from mice that were prone to developing skin cancer, the incidence of skin cancer among the animals dropped significantly. Injecting the animals with B cells from other mice restored the telltale signs of chronic inflammation and cancer. Coussens found that the B cells do not actually infiltrate the premalignant tissue. Instead, they work remotely, sending signals through the blood to other immune cells that do their bidding. Those cells, once chronically engaged, help establish an environment that favors tumor growth, says Coussens.

Coussens, whose lab also studies lung cancer and breast cancer, hopes her results in mice will translate to humans. If so, one idea would be to give patients a drug that acts on B cells in the body. Such therapy could be used to prevent skin cancer or other types of solid tumors from developing in patients at risk for the disease. Or, it could be used to treat patients after they’ve had a tumor surgically removed to prevent the cancer from recurring. “That would be the perfect outcome,” says Coussens.

Anti–B cell drugs already exist, she notes. The biotech firm Genentech currently markets a drug called Rituxan (rituximab) for treating patients with non-Hodgkin lymphoma and rheumatoid arthritis. “So the question is: Are there human solid tumors like we’ve seen in mice that are positively regulated by these same mechanisms?” says Coussens. “If there are, can we identify them and can we identify which patient [groups] might benefit from that kind of therapy that’s already proven safe?”

KITCHEN CURES
Effectively preventing cancer in patients at risk will require not just safer and more effective drugs but compounds that are cheap and can be taken over a long time. That’s why many researchers are focusing on natural compounds. For instance, C. Richard Boland, the chief of gastroenterology at Baylor University Medical Center in Dallas, recently conducted laboratory studies that suggest a compound present in a variety of apple may reduce the risk of colorectal cancer.

Several years ago, chemists at the University of Naples in Italy were trying to identify which components of the Mediterranean diet explained the lower incidence of cancer in southern Italy compared with northern Europe. The Italian researchers homed in on Annurca apples, a variety from southern Italy, and extracted from them natural chemicals known as polyphenols. These plant-derived molecules have been linked to various health benefits from delayed aging to lower rates of cardiovascular disease. The researchers then asked Boland’s team to test their polyphenol extract in colorectal cancer cells. “So we put it into some cultures, and it turned out it killed cancer cells,” says Boland. Initially, he was not impressed since countless things kill cancer cells in the lab. It wasn’t until his team uncovered the polyphenols’ mode of action that Boland got excited.