A New Strategy in the War on Cancer: A Lesson From WW II –“Bomb the Runway”
By John Maa
Contributing Writer
A new direction to combat cancer was revealed to me recently as I sat by the gate waiting to change planes in the airport in Phoenix.
An Army pilot from World War II was seated next to me – he was en route to his 87th birthday party in San Francisco. He described his experiences in the air battles of the South Pacific – I asked him how many enemy planes he had destroyed, and he said there were too many to count. I then asked him what it felt like to shoot down an enemy fighter plane in air, and interestingly, he said he had actually only fired at planes stationed on the ground. He then shared the Allied strategy to military success in attacking an air installation – which presents a novel strategy in the “war against cancer.”
The key question: Of the potential targets available when attacking an enemy airfield – which should be destroyed first? The intuitive possibilities include the hangar where the planes are housed, the soldier’s barracks, the control tower or perhaps the gun emplacements?
The answer is none of the above, and perhaps counterintuitive. The correct answer reflects experience, and a brilliant military strategy. The valuable lesson learned by the United States Army Air Corps – was to always bomb the runway first. The orders to the pilots were always the same – the heavy bombers would first destroy the landing field, then the smaller fighters would follow and destroy the planes on the ground, the control tower, and all of the other important military targets at will. Once the runway had first been destroyed, the enemy pilots on the ground could not man their planes, launch a counteroffensive or escape.
Extend the analogy of destroying an enemy airfield to cancer for a moment. The key goals include destroying 1) the primary tumor, and 2) its site of metastasis (how it spreads and often escapes cure).
A critical step to the success of a cancer is the ability to metastasize – to invade through the basement membrane and take up residence elsewhere in the body. In addition to being immortal, metastasis is a unique property of cancer cells which normal cells don’t display. Our normal lung cells don’t travel to the brain, and liver cells don’t implant in the lung. The process of cancer spread requires the tumor to take off on its unique runway.
In the war against cancer, we have yet to apply the valuable lessons of World War II – we have not targeted the unique cellular mechanisms which allow tumor cells to metastasize. This singular property of cancer cells which enables them to spread, may also prove to be their Achilles heel.
Two broad strategies present themselves:
Plan A: Link a toxin (such as ricin) with an antibody to the specific cell surface receptors and ligands involved in metastasis – to induce apoptosis in the cancer cell.
Plan B: An alternative is to block primary tumors from the ability to metastasize, so that the primary tumor can be contained, and is amenable to surgical resection
Some interesting observations and questions from the oncology literature:
1) Where is a tumor most likely to metastasize to? The answer may be: back to the site of the primary tumor, suggesting the existence of some kind of landing mechanism/ cell surface receptors which attract tumor cells back to their site of origin.
2) Do metastases metastasize? The answer is unknown, yet it is likely that both the primary site and nodal metastases can serve as sites of spread – a strategy similar to “island hopping” during WW II.
3) Why don’t cancers metastasize to the heart? Likely because there is no runway for the tumor to achieve a safe landing – the turbulent effects of the constant bloodflow preclude adherence.
4) Preliminary data suggest that micro RNA’s may be differentially expressed in cells that are metastatic, compared to either healthy or non-metastatic tumorigenic cells. miRNA’s may provide a clue to elucidating the key mechanisms of metastasis and colonization.
Judah Folkman’s strategy of blocking angiogenesis was reasonable, but likely too late. Blocking blood vessel ingrowth to a metastatic tumor would be futile – akin to a strategy of preventing enemy planes from refueling after they have already escaped and are in the air fighting back…
Additionally, his strategy did not target a property unique to cancer cells, as normal regenerating cells also require angiogenesis to survive.
The ability to cure pancreatic, colorectal, lung, prostate, gastric and breast malignancies is critically dependent upon diagnosis and surgical intervention before the primary tumor has spread. Applying the military air strategy from World War II, perhaps one day we can confine human cancers to their primary site by disabling their cellular mechanisms to “take off their runway” and metastasize, and then utilize a combination of surgery, chemotherapy, and radiation therapy to annihilate the primary tumor at will.
John Maa, MD, FACS, is an Assistant Professor, UCSF Department of Surgery.
This article appeared in the November 12, 2009 issue of Synapse.
