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Fighting Cancer by Dr. David L. (“Woody”) Woodland (as published in the Summit Daily News of July 27, 2015) Cancer presents itself in many different forms and attacks people from all strata of society. A cancer diagnosis is something we all fear, since mortality rates can be high depending on the type and stage. Consequently, the disease has been the focus of intensive research for decades, and there have been tremendous advances in our understanding of its underlying biology. Indeed, effective treatment options are now available for many of its forms, although these mostly involve chemotherapeutic drugs or radiation and their associated side effects. But recently, there has been growing excitement around the idea of harnessing the body’s own immune system to fight cancer. This is not a new idea; however, only in the last few years have scientists begun to understand the cues the body needs to engage the immune system. The immune system is designed to sense anything foreign in the body, such as a bacterium or virus, and then martial forces to eliminate that agent. This is why we recover from illnesses such as strep throat and flu. Importantly, the immune system is able to distinguish the body’s own cells (“self”) from invading agents (“foreign”), allowing it to focus its destructive power on the invading agent. The immune system is also perfectly capable of eliminating cancer cells, yet in many cases it just seems to stand by and ignore the problem (i.e., treat the cancer cells as “self”). There are several reasons for this. First, some cancer cells are almost indistinguishable from healthy cells; after all they are essentially just uncontrolled outgrowths of otherwise normal cells. The immune system has great difficulty “seeing” these cells. Second, even though some cancer cells contain plenty of abnormal proteins identifying them as “foreign” with respect to other cells, the immune system still fails to attack because it lacks evidence that the foreign agent is a bona fide infection. Most infectious agents induce specific types of inflammatory responses that alert the immune system to wake up and attack foreign agents. But cancer cells do not typically send out the necessary inflammatory signals, so the immune system remains inert and fails to respond. It has been clear to clinicians for some time that we simply need to wake up the immune system, helping it to recognize and respond to cancer cells. This area of research has expanded tremendously in recent years and is now referred to as “cancer immunotherapy.” One of its earliest examples was the use of “Coley’s toxins” to treat cancer. This was the discovery by William Coley early last century that a vaccine comprised of killed bacteria could sometimes cause tumors to regress. Scientists now believe that the killed bacteria provided the inflammatory signals necessary to wake up the immune system so that it could attack cancer cells containing abnormal proteins. However, this treatment was very crude and was associated with numerous side effects (it is still used today in some circumstances but is not approved by medical authorities). Nevertheless, it provided a template for future study. Today, there is a range of new therapies being developed that are designed to stimulate the immune system to target and kill cancer cells. One of the first medically approved treatments involves isolating white blood cells from the patient and exposing them to proteins that are abnormally expressed in the cancer cells. The cells are then given inflammatory signals to activate them prior to their transfer back into the patient, where they trigger the immune system to seek and destroy the cancer cells. Another approach under development involves throttling down regulatory mechanisms that tend to inhibit triggering of the immune system. The goal is to make the immune system more sensitive to activation signals by lowering the threshold needed to attack cancer cells. Finally, researchers have recently developed a novel approach to treating otherwise inoperable malignant melanoma. In this case, the patients were infected with a genetically modified version of a herpes virus that specifically attacks the melanoma cells. The virus killed some of the melanoma cells but also provided all of the signals necessary to activate the immune system to finish the job and eliminate any remaining melanoma cells. It seems likely the treatment will receive approval in both Europe and the United States. There are many additional cancer immunotherapy treatments in the pipeline that use novel approaches to trigger the immune system to attack cancer cells, engendering considerable excitement in clinicians and patients alike. These developments illustrate the power of basic and applied research in developing innovative new treatments for complicated diseases. They further demonstrate the power the body has to heal itself... apparently it just needs a few nudges in the right direction. David L. Woodland David L. “Woody” Woodland, Ph.D. is the Chief Scientific Officer of Silverthorne-based Keystone Symposia on Molecular and Cellular Biology, a nonprofit dedicated to accelerating life science discovery by convening internationally renowned research conferences in Summit County and worldwide. Woody can be reached at 970-262-1230 ext. 131 or [email protected]. For more (Petri) Dish columns, visit www.keystonesymposia.org.