This new view implies that rooting out every last cancer cell in the body might not be necessary. Anti-inflammatory cancer therapy instead would prevent premalignant cells from turning fully cancerous or would impede an existing tumor from spreading to distant sites in the body. Cancer sufferers might then be able to survive, in the same way that new drugs have let HIV patients live longer. “I don’t think a cure is necessarily the goal. It doesn’t need to be,” comments Lisa M. Coussens, a cancer biologist at the University of California, San Francisco. “If you can manage the disease and live your natural life span, that’s a huge win.”
Multiple Lines of Defense
Comprehension of the link between inflammation and cancer requires knowing how the body reacts to invaders—and how normal healing is then subverted into promoting cancer when the inflammatory state lasts too long. After you step on a nail, the bacteria that invade the sole of your foot receive a welcome from an array of proteins and white blood cells that resemble rejects from central casting for the movie Creepshow 2. Just one example: Some 20 complement proteins, so called because they complement other bodily defense mechanisms, chemically spritz pathogens until the invaders explode into a big protoplasmic mess. While the complement system slimes the area, an assemblage known in immunology textbooks as professional phagocytes—literally “expert eating cells”—goes to work.
Lacking table manners, these Pac-Man-like macrophages and neutrophils proceed to engulf and consume the uninvited guests. Other members of the attack brigade include natural killer cells, mast cells and eosinophils. Healing represents more than launching an offensive against invaders. Blood platelets involved with clotting migrate to the break in the skin from an inner layer infused with blood vessels. Enzymes direct the repair of the extracellular matrix, the protein-based mortar in which the cells are immobilized. A scab forms, the skin grows back and the whole process of inflammation ends. Sometimes, though, inflammation does not stop. Any tissue (not just skin) that is chronically inflamed because of the persistent presence of pathogens, toxins or genetic damage helps to spur illness, from heart disease to cancer.
Beyond this first layer of defense, vertebrates are equipped with additional weaponry. The adaptive system learns an invader’s specific molecular signature and then uses it as a target for killing. Among the protagonists are B cells, which produce antibody molecules able to neutralize pathogens or mark them for destruction, and T cells, which prompt infected cells to kill themselves or secrete chemicals that direct the activities of other immune players.
In recent years a body of evidence has accumulated to show that chronic inflammation can play an important role in the progression of some types of tumors from a premalignant state to full-blown disease. A link between cancer and inflammation has long been suspected. In 1863 the prominent German pathologist Rudolf Virchow noted the presence of so-called lymphoreticular infiltrate (white blood cells) in malignant tissue. As early as 1978 Alberto Mantovani of Humanitas Clinical Institute and the University of Milan had observed that innate immune cells tend to congregate around some tumors. Cancer biologist Harold F. Dvorak of Harvard Medical School remarked in 1986 that tumors are “wounds that do not heal.” The status quo, though, lay elsewhere. Even a decade ago many biologists still hewed to the idea that the immune system serves not only to eliminate pathogens but to ferret out cells that are the abnormal precursors of cancer. But a closer look at the microenvironment surrounding tumors found the unexpected.
Hunting Pigeons
In the late 1990s Frances Balkwill of the Institute of Cancer at Queen Mary, University of London, had been doing research on a cytokine (a hormonelike immune signaling molecule) known as tumor necrosis factor (TNF), which was named for its ability to kill cancer cells when administered directly into a tumor at high levels. But when TNF lingers as a chronic, low-level presence in the tumor, it acts very differently. Balkwill’s lab turned off the TNF gene in mice so that the rodents could not produce the protein: to their surprise, the mice did not contract tumors. “That really put us as the cat among pigeons,” she recalls. “All the people who were working on TNF as an anticancer agent were horrified. This cytokine they thought was a treatment for cancer was actually working as an endogenous tumor promoter.”
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5 Comments
Add CommentThis actually is not new news.. the theoretical model in Traditional Chinese Medicine ascribes the precursor to cancers as being "heat toxins" which can be loosely described as free radicals causing an inflammatory response in the body. A survey of herbal treatments for this condition may provide indicators for new pharmacologically active compounds that could prevent/protect the body from carcinogenic cellular growth
Reply | Report Abuse | Link to thisMany of the parasites which can colonise the human body influence our immune systems and dampen our inflammatory response to make us more hospitable hosts. I wonder are there any such organisms already producing their own ready-made pharmaceuticals which we could benefit from in this way to make us less susceptible to cancers and other inflammation-mediated disorders?
Reply | Report Abuse | Link to thisMany physicians believe that cellular inflammation is the basis for many of the common degenerative diseases that are impacting our population. With a host of information on anti-inflammatory supplements and diet guides, it just makes sense to pursue an anti-inflammatory lifestyle.
Reply | Report Abuse | Link to thisThere are indeed therapies based on helminths (hookworms) that offer promise. Sadly, however, this has not received much funding or media attention, likely because of the aversion of some to the idea of having living parasites in their body. The University of Iowa and Nottingham University in the UK have been two centers of study for helminth therapy.
Reply | Report Abuse | Link to thisHopefully soon helminth therapy will become more widely studied and available.
Thank you for such a great summary of Chronic Inflammation in Cancer study. It is very use to take information from cross-disciplines and apply it to your research such as Tissue Engineering/Regenerating tissues. Interestingly macrophage polarization determines positive regeneration or chronic inflammation and some of the information obtained in cancer studies can be borrowed to regenerate tissues & organs.
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