only a few molecules are needed to kill a cell. Cancer cells lacking the appropriate cell surface molecule (or which have it, but can’t internalize the lethal payload) will resist this line of attack.
Siege Warfare and Naval Blockades = Angiogenesis Inhibitors
Picture a medieval castle under attack, surrounded by an army that prevents food (and other supplies) from reaching those living inside the ramparts. Starving your enemies can be an effective approach to killing them off, or at the very least, preventing them from spreading. Naval blockades do the same thing if they can successfully prevent an enemy from being resupplied, as was done against the South during the Civil War.
Cancer drugs known as angiogenesis inhibitors (e.g. bevacizumab (Avastin)) employ this concept as a therapeutic approach. They block the development of blood vessels within growing tumors, which in turn reduces the flow of nutrients in the bloodstream to the cancer cells. These treatments are better at slowing down the growth of tumors than eliminating them.
Recruitment of Resistance Fighters = Immunotherapy
Imagine being able to train the local populace to recognize, attack, and kill invading enemy soldiers they encounter in every city, village, and house. This would be an ideal way to deal with an occupying army, but there are two challenges here. The first is developing an effective training procedure so that the fighters are skilled enough to achieve their mission, and the second is being able to recruit a sufficiently large number of these home-grown fighters to fully engage the enemy.
This is the concept that immunotherapy approaches (e.g. ipilimumab (Yervoy)) bring to the cancer battle. The idea is to train the immune system to recognize and destroy cancer cells wherever they are hiding in the body. There are many technical challenges with this approach, but the essential problem can be simply stated: the correct cells must be recognized and eliminated, and you cannot mis-identify normal cells and kill them as well.
Deny Access by Blowing Up the Bridges = Viral Vaccination
One effective approach to protecting the homeland is to prevent foreign troops from invading in the first place. Set up a defensive system so that the invaders cannot establish a beachhead on your terrain, and you won’t need to fight them in the streets later on. One way to do this is to dynamite the bridges and tunnels that could be used to access your territory.
This is the basic idea behind immunizing young women (and men) against human papilloma viruses (e.g. Human Papillomavirus Quadrivalent Vaccine (Types 6, 11, 16, and 18) Vaccine, Recombinant (Gardasil)). Infection by certain strains of papilloma virus can eventually lead to cervical cancer in women and other types of cancer in men. People who are successfully immunized are resistant to the viruses and won’t develop these cancers later on. Unfortunately, there are very few cancers whose growth is thought to be initiated by viral infections. As a result, this approach wouldn’t work against a large number of different tumor types.
Assassinate Enemy Leaders = Kill Cancer Stem Cells
If you can kill the leaders of the enemy army, you will seriously weaken it and will have a much easier time fighting the remaining troops. The primary goal here is to find, identify, and extirpate these top commanders, who are often hidden away and difficult to locate. They also have been known to employ doppelgangers to draw attention away from the real individuals, further complicating the task of finding them.
There is a parallel to this strategy in cancer therapy: try to eliminate cancer stem cells. These cells are posited to be the source of all of the other cancer cells, and it is believed that eliminating these rare cells might be a successful treatment strategy. As with some of the other approaches described above, the challenge is to identify and destroy these cells without wiping out a significant number of normal cells. While there are no medicines currently on the market using this approach, some companies (e.g. Verastem) are focusing on this drug development strategy.
Blitzkrieg = Combination Therapy
This is an all out attack on the enemy in which you attempt to overwhelm it by using a massive display of force in a short time period. In many of the scenarios I have described above, the enemy’s strategy evolves in response to the attack so that it is no longer effective. If you want to avoid the development of a resistance movement, or block your enemy from re-arming, a blitzkrieg attack might do the trick.
Combination treatments (e.g. folinic acid/fluorouracil/irinotecan/oxaliplatin (Folfirinox)) are the blitzkrieg approach in cancer therapy. Employing multiple drugs at the same time to kill off tumor cells can be effective at
