viernes, 1 de mayo de 2015

viernes, mayo 01, 2015
 
The Future of Cancer: Closer to a Cure
 
Sloan Kettering CEO Craig Thompson on the revolution under way in cancer prevention and treatment
 
By Craig B. Thompson
          
 
            
That may be true, but it doesn’t mean getting cancer is inevitable. The fastest and most extensive rates of cell division occur when we are developing as embryos. Billions upon billions of cells are produced each day, yet cancer in newborns is exceedingly rare. In contrast, cell division in each of our tissues slows as we grow older, while the incidence of cancer increases with age.

We damage ourselves

What accounts for this discrepancy? One overlooked factor is that during pregnancy, both the mother and the placenta protect the developing embryo from environmental exposure. In contrast, we constantly put ourselves in harm’s way as we age. We are exposed to viruses and bacteria that damage our tissues. And it isn’t just invading pathogens that wreak havoc; we do most of the damage ourselves. Through sunburns, smoking, environmental pollutants and overeating, we constantly damage our tissues, forcing restorative cell proliferation to occur in a war zone of damage.

It is in this inhospitable environment that most cancers arise. We have known for some time that many of these environmental exposures damage DNA, making it harder to copy and resulting in more mutations as cells divide. Recently, we have come to appreciate that during regeneration of damaged tissue, the rest of the body pitches in to keep every cell in the damaged tissue alive. Not just the healthy cells, but also the ones that have acquired mutations that render them unfit. Our immune system, which usually detects and destroys cells with excess mutations, is turned off. The body produces growth factors that stimulate the survival of cells with deleterious mutations, and our habit of overeating maintains an excess supply of nutrients that compounds the damage.

These are scientific facts we didn’t appreciate even a decade ago. But how can this information be harnessed into better cancer treatment and prevention?

Some of it is clear. Don’t smoke, use sunscreen, avoid unnecessary radiation exposure, get vaccinated. Sometime this decade, it is expected that obesity, driven in large part by excess sugar intake, will surpass tobacco exposure as the No. 1 cause of preventable cancer in the U.S. Already, in terms of population health, we are putting this new scientific knowledge to use. Earlier this year, new guidelines to reduce the percentage of sugar in our diet were added.
 
 
 
Precision medicine

This new information is also revolutionizing cancer care. Until recently, cancer was treated based on the tissue in which it originated. Increasingly, effective cancer therapy is empowered by knowing the precise mutations a patient’s tumor has acquired, independent of where in the body the cancer arose. This approach is called precision medicine.

Patients whose cancer bears specific mutations are now more effectively treated with drugs designed to selectively reverse the effects of those mutations. Such drugs are termed targeted therapeutics. The downside of this class of drugs is that they usually don’t have any benefit in treating cancers that don’t carry that specific mutation. While we don’t yet have many therapies that target cancer-causing mutations, the results can be dramatic when such drugs are available.

We have learned that the number of mutations a cancer cell has acquired also matters. Our immune system is designed to recognize cells with new properties, as when infected with a virus. The mutations building up in a cancer cell are exactly what our immune system should respond to. The more mutations there are, the more likely it is that the immune system can recognize and destroy the cancer cells.

A recent discovery has unlocked this potential. Immunologists have found that our immune system has a built-in “off switch,” a checkpoint that shuts down an immune response a few weeks after it is initiated. A new and expanding class of cancer therapeutics have been developed that have the ability to block this normal shut-off switch and thus augment the ability to recognize and destroy cells carrying mutations. In the right situation, “immunotherapy” can have stunning efficacy. Some patients with widely metastatic cancer have been rendered cancer-free with therapies aimed at increasing the body’s own ability to fight cancer.

Missed signals

Our knowledge of cancer is still expanding. We have begun to appreciate that cancer is initiated primarily in the cells that endow us with the ability to repair our tissues. When a tissue is damaged, so-called progenitor cells expand in number to fill the damaged area, and once that is accomplished, the cells differentiate to form tissue much like the original. Some of the mutations discovered in cancer cells result in the signal to differentiate not being received or acted upon. As a result, progenitor cells keep on reproducing.

Treatments that focus on restoring a cell’s ability to differentiate, thus stopping the excessive proliferation, are already being used successfully in the clinic. These therapies avoid the toxic side effects of traditional chemotherapy and can effectively eliminate cancer cells even when they have spread throughout the body.

Why is finding a cure for cancer taking so long? A major reason lies in the fact that cancer is not one disease, but many. Each tissue has its own unique progenitor cells, and each tissue uses only a subset of the genes we inherit from our parents; each tissue is exposed to environmental insults differently. We are just beginning to understand the interplay of all these factors in the origin of the many forms of cancer. Understanding these issues will ultimately allow us to optimize the treatment approach to each patient’s disease.

While we aren’t yet ready to put cancer on the extinction list along with “simpler” diseases like smallpox and polio, it is clear that with more science—the lessons learned from cancer research over the past two decades—we face the future with less fear.


Dr. Thompson is president and chief executive officer of Memorial Sloan Kettering Cancer Center in New York. He can be reached at reports@wsj.com.

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