Military Strategies Being Used in the War on Cancer

8/4/14

Nearly everyone has heard of the War on Cancer, which was launched during the Nixon administration with the passage of the National Cancer Act of 1971. The goal of this legislation was to eradicate (or at least significantly decrease) the number of U.S. cancer deaths. Progress in meeting this goal has been slow over the past 40 years. Sadly, we lose more of our citizens to cancer every two years (an estimated 1.14 million) than the total number of military casualties suffered by our troops in the entire history of our country (about 850,000 men and women). Like many wars, this one turned out to be much tougher to win than many people thought it would when the NCA was set into law.

Advances in molecular biology, biotechnology, and genomic sequencing have contributed significantly to the discovery of the molecular cause of a wide variety of cancers in recent years. Multiple DNA analyses have shown that cells within the tumor mass generally contain a large number (tens to hundreds) of different mutations. The changes seen in one cell are often distinct from those observed in distant cells, making each individual tumor that much more difficult to treat. Despite this heterogeneity, genomic sequencing of different cancer types has also revealed that individual tumors share an attribute of snowflakes: while they are all uniquely different, they also share some similar features. Common mutations have been found across many different types of cancer. This suggests that drugs that were originally designed to treat just one specific type of cancer might work on different tumor types as well. This idea is being tested in a number of clinical trials as part of a precision medicine approach to treating cancer.

Despite these developments, many people don’t have a good understanding of how drugs that fight cancer work, and what their limitations are. A recent article in the New England Journal of Medicine reported that a majority of late stage colon and lung cancer patients didn’t understand that the chemotherapy used to treat their disease would likely not cure them. Clinical cancer trials are not designed to be treatments per se (which is why they often have placebo or “current standard of care” control groups) but to gather information that may be helpful down the line for the treatment of others. The approaches taken by many anti-cancer treatments actually have strong parallels to a variety of classic military strategies. Comparing these different tactics side by side (and in a simplified way) may help illuminate how these cancer therapies are designed to work.

Aerial Bombardment and Artillery Fire = Surgery

If a small number of enemy troops invade your territory, it may be possible to wipe them out with aerial bombs or artillery fire if they’re concentrated in a small area. To be most effective, you need to make sure that all of their troops are killed. If a few escape, they can spread to other areas where they can cause problems in the future. If the escaped troops have spread out sufficiently, then it may be impossible to eliminate them entirely.

Surgery is an effective way to remove tumors when they are still small, have not metastasized to distant sites, and are in a part of the body where they can be readily accessed. Unfortunately, many tumors at the time of diagnosis have already spread throughout the body or are inaccessible, meaning surgery won’t cure these patients.

Poison Gas Attacks = Chemotherapy (and Radiation)

Picture the bleak, cratered landscape of a muddy World War I battlefield, with both sides huddled down in their respective trenches. The German artillery launches shells containing mustard gas in the direction of Allied troops. This poison’s been designed to kill or disable large numbers of soldiers, but once it’s released, it can’t discriminate between French and German troops. Though targeted at the enemy, the gas can inflict serious collateral damage on the attacking troops if the wind blows in the wrong direction. It’s major failing as a weapon: it can’t distinguish friend from foe.

Many chemotherapy drugs act in this same indiscriminate way, and some of them, the nitrogen mustards, are chemically related to the poison gasses used in the trenches. These drugs (e.g. Melphalan) kill actively dividing cancer cells by cross-linking their DNA strands. However, their effects are non-specific. They will indiscriminately kill off many other types of actively dividing cells, such as those in your hair follicles or that line your intestines. These therapies can’t be given at too high a dose or they will kill the patient. Radiation therapy works in a similar manner to chemotherapy in the sense that it also damages DNA and it is not possible to only target cancer cells with it. Radiation can sometimes be focused on a limited treatment area, but it can’t distinguish between normal and cancer cells.

Slow The Enemy’s Advance = Enzyme Inhibitors

Visualize an enemy army that has invaded your country, and their troops are marching onward, spreading death and destruction in their wake. You want to kill the invaders, but your armories have been depleted of their most effective weapons. In this situation, slowing down the advance of your enemy can be an effective strategy while your factories work overtime to rebuild your munitions or develop new and effective weapons.

Anti-cancer drugs that function as enzyme inhibitors (e.g. imatinib mesylate (Gleevec)) work in this way. They kill (or at least slow the growth) of your cancer cells by inhibiting the activity of enzymes that play an important role in cell growth. Unfortunately, they also put selective pressure on the population of cancer cells that, as a result of chance genetic mutations, have a slightly different form of the enzyme. These cancer cells may become resistant to the original drug and multiply. If you’re fortunate these mutated cells may still be … Next Page »

Stewart Lyman is Owner and Manager of Lyman BioPharma Consulting LLC in Seattle. He provides strategic advice to clients on their research programs, collaboration management issues, as well as preclinical data reviews. Follow @

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