Laying Siege to Cancer

Cancer is an infinitely cunning disease. It contrives to hijack most every system of the body to support its own survival, from an individual cell’s energy production all the way to the body’s entire circulatory system. This devious nature is what makes cancer such a difficult disease to treat: to fight it, we have to fight ourselves. A new study out of the University of Washington has found a way to do just that, to attack cancer via its own wily maneuvers by targeting its commandeered support system rather than the tumor itself.

To survive, tumors need to go to great lengths to both keep the body at bay and to supply themselves with large amounts of energy. A group of immune cells, called Tumor Associated Macrophages (or TAMs, for short), help cancer cells on both of these fronts. Under normal circumstances, these TAMs are known as M2 macrophages, and their job is to help shut down an inflammatory response. When the body has successfully ousted some bacterial or viral invader, the immune system needs to be able to stop its attacks, or else inflammation would never end (a very unpleasant situation to be in). Normally, M2 macrophages are responsible for this process.

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A mouse macrophage consuming two particles (Source: en.wikipedia.org)

When they are recruited by tumors though, this ability is diverted towards preventing an immune response against the malignant growth. So any attempt by the body to defend itself is quickly stopped by its own feedback system, which then keeps the tumor safe to continue growing. At the same time, these recruited macrophages help to promote what is called angiogenesis, or the creation of new blood vessels. These vessels feed blood and nutrients directly to the tumor, helping to meet its considerable energy needs.

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Process of angiogenesis in tumors (Source: http://www.angioworld.com)

Researchers at the University of Washington recognized how pivotal these TAMs could be, and decided to design a new treatment that would target them in place of the tumor. They attached a specific peptide sequence to another protein known to bind easily to the TAMS, which allowed them to get that first, very special little peptide sequence inside the tumor-supporting cells. Now what is so special about this peptide sequence? Well its name is KLA and it triggers apoptosis, which is a cool-sounding way of saying programmed cell death. Apoptosis is how your body kills off old and dysfunctional cells. It amounts to a cellular fail-safe that, when activated, causes the cell to systematically kill itself. So just think of the whole process like a Bond movie: sneaking a nuclear arms expert into the villain’s lair to disarm some hijacked nuclear array. It’s the same basic concept, just on a much smaller scale, and I get to say apoptosis, which is fun for me.

The experiment succeeded in getting this dangerous peptide exclusively into the TAMs (meaning all other cell types are safe from its effects), which subsequently lengthened the life of those mice treated while also showing significant decreases in tumor growth compared to untreated mice. The success of this experiment highlights something very important about cancer. Cancer’s greatest strength is its ability to seize control of the body’s own support systems. But this process is also one of its greatest weaknesses. Cancer has a lot of needs, most notable (in this case at least) defense and energy. It cannot thrive without using the pre-existing bodily systems, which leaves it vulnerable. If you cut off the supply lines, even cancer can’t survive. Cancer is cunning and dangerous, but it is not self-sufficient. And that is a very good thing for us.

Original article: http://www.pnas.org/content/110/40/15919.full

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