Cancer Blockers
The recognition that cancer is more like an organ than just a clump of cells with DNA mutations in cell nuclei may also explain why some of the previous approaches to chemotherapy have met with limited success. “People have taken cells and then transformed them in culture and stuck them into animals,” Pollard says. “They grow as little balls. They do certain things there. But they are not complex tissues, whereas a naturally occurring tumor is a very complex tissue.”
Instead of just killing cancer cells—the goal of current drug therapies and radiation—new approaches may supplement existing drugs by slowing inflammation. Without the involvement of macrophages and other innate cells, the premalignant tissue would remain in check.
Cancer could, in essence, become a chronic disease akin to rheumatoid arthritis, another inflammatory condition. “Keep in mind almost no one dies of primary cancer,” says Raymond DuBois, provost of the University of Texas M. D. Anderson Cancer Center and a researcher of anti-inflammatory agents for cancer. “A patient almost always dies from a metastasis.”
A pharmaceutical against chronic inflammation represents a more alluring proposition than massacring malignant cells (and, unavoidably, healthy ones), a consequence of existing chemotherapies. Taken alone, such an agent might be benign enough to use every day as a preventive for high-risk patients. Epidemiological and clinical studies have shown some promise for the use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin to stave off the onset of some solid tumors. Investigations continue on more selective blocking of the production of prostaglandins, the regulatory molecules that are curtailed by NSAIDs. In particular, drugs that inhibit production of prostaglandin E2 may curb inflammation and tumor growth, while avoiding the cardiovascular side effects of drugs such as Vioxx and the gastrointestinal problems of the earlier class of NSAIDs [see “Better Ways to Target Pain,” by Gary Stix; Scientific American, January 2007]. The anti-inflammatory effects of the ubiquitous statins used to lower cholesterol are also being contemplated.
Some treatment options already exist. The drug Avastin inhibits production of the angiogenesis- promoting VEGF, although oncologists must contend with other molecules in the tumor microenvironment that promote blood vessel growth. Drugs developed for more familiar inflammatory diseases may also fight cancer—and these medicines might be combined into HIV-like drug cocktails, that also include angiogenesis inhibitors and cell-killing agents.
Inhibitors of TNF have received approval for treatment of rheumatoid arthritis, Crohn’s disease and other disorders and are now in clinical trials for both solid tumors and blood cancers. The drug Rituxan, a monoclonal antibody that represses B cells in rheumatoid arthritis and B cell lymphoma, might prevent the inflammatory response that fuels formation of solid tumors. Other cytokines and related molecules (IL-6, IL-8 and CCL2, among others) are also potential targets, as is NF-KB.
Some existing compounds, including NSAIDs and even one found in the spice turmeric, exert at least some of their effects by inhibiting NF-KB. But major pharmaceutical laboratories are investigating highly selective inhibitors of this molecular linchpin, many of them targeted at the enzymes (such as I-KB kinase) that regulate NF-KB activity.
A Chemical Trojan
One group is contemplating a radically ambitious treatment, a molecular Trojan horse of sorts. Claire Lewis and Munitta Muthana of the University of Sheffield in England and their colleagues have designed a drug delivery scheme that takes advantage of the natural attraction of macrophages to the oxygen-starved areas in tumors. They have engineered macrophages to deliver a therapeutic virus to hypoxic tumor regions, which respond poorly to conventional treatments such as chemotherapy and radiation because of an insufficient blood supply. Once the macrophages arrive in a tumor (grown in culture so far), each one releases thousands of copies of the virus, which then infect the cancer cells, after which a protein in those cells activates the therapeutic gene in each virus. This action then directs synthesis of a cell-killing toxin. “The macrophage is migrating into a site and doing what we want it to do rather than driving tumor development in a normal way,” Lewis says.
See what we're tweeting about
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.
Reply | Report Abuse | Link to this