The Future of Cancer: Closer to a Cure
Memorial Sloan Kettering Cancer Center CEO Dr. Craig Thompson tells WSJ’s Simon Constable why he’s optimistic about new therapies aimed at increasing the body’s own ability to fight cancer. Photo: Andrew P. Leonard/Hanna Irie, MD, PhD, Mount Sinai, NY, NY
Decades into the declared modern war on cancer, scientists and clinicians are excited by what we are learning. Yet patients and families are too often frustrated by the lack of progress in prevention and treatment.
To understand this seeming paradox, we have to consider what has been learned about the biology of cancer and how we are putting this knowledge to use.
Viewed in this light, there is tremendous hope for the future, both in decreasing an individual’s lifetime risk of getting cancer and in increasing the success of treating those cancers that do arise.
Most people don’t acquire a significantly higher risk of cancer from the genes that they inherit from their parents. Instead, cancer arises as a result of copying errors (mutations) in the inherited genes, as our bodies make new cells to maintain our various organs. A recent widely quoted publication suggested that these errors are an inevitable consequence of trying to copy three billion bits of information as a cell divides.
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.
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.
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.
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