According to the American Cancer Society, an expected 1.5 million new cancer cases will be diagnosed in the U.S. this year, and around 500,000 Americans will die from cancer—more than 1,500 per day. Cancer is the second most common cause of death after heart disease, resulting in almost 25 percent of all deaths in the U.S.
But talking about “cancer” may be misleading.
According to oncologist Michael Gallagher we should probably talk about “cancers” instead of “cancer.” “There is no one mechanism that all cancers have; it’s a very varied disease,” says Gallagher, medical director of the Sparta Cancer Center in New Jersey. “Breast cancer,” for example, refers to the collection of cancers that occur in the breast; but on a molecular basis, there are at least five different subtypes of breast cancer that operate differently and require different treatments.
Though the media hype about new cancer treatments and the dream of a “cure” may exaggerate the results of cancer research, the progress is nonetheless real and striking.
“We understand cancer infinitely better than we did just a decade ago, but I think we’ve just begun to scratch the surface,” explains Gallagher. “The rate of discovery is increasing exponentially.”
Cancer research has led to new treatments that target the specific molecular processes involved in cancer progression, as well as the specifics of an individual’s cancer. But more than that, Gallagher notes, we may see a change in the way doctors and patients view cancer that will transform the future of cancer research and the lives of individuals suffering from the disease.
Cancer cells differ from normal cells in various ways, including their ability to replicate without limit, avoid cell death, and create blood vessels for oxygen. Because these processes require molecules like proteins or hormones, one new trend in cancer treatment involves trying to interfere with these molecules by using targeted therapies.
In contrast to chemotherapy or radiotherapy, which traditionally affect normal cells as well as cancer cells (although innovations are changing this), targeted therapies can be more effective and less harmful to the patient because they specifically act on cancer cells.
In some breast cancers, for example, the cancer cells have estrogen receptors that, when bound to estrogen, result in cell growth and proliferation. The breast cancer drug tamoxifen binds to the receptor and prevents estrogen from binding to it.
Because cancers vary, however, we need ways of detecting the proper molecular “target” for these therapies and predicting whether the patient will respond to them.
“We recognize that every individual has a genetic makeup and every cancer has a genetic makeup,” says Gallagher. “We would personalize the dosing and the drug to the disease and to the patient.”
To do this, researchers use what are called biomarkers. In the case of cancer, biomarkers refer to substances, produced by cancer cells or the body in response to cancer, that identify or “mark” the specific type of cancer a patient has. They can be measured by blood, urine, and tissue tests.
“The rate of discovery is increasing exponentially.”
In the breast cancer example above, tissue samples could determine whether a patient’s cancer cells have estrogen receptors. Next, however, doctors must determine whether the drug tamoxifen would be effective on the patient in question. Tamoxifen must be metabolized by the enzyme CYP2D6 into a different substance to be fully effective; an abnormality in the CYP2D6 gene—a biomarker detected by a blood test—would indicate that tamoxifen therapy would likely be ineffective. This form of personalized medicine, which relies on genetic variations in the patient, is called pharmacogenomics.
“We’ve got great drugs out there; we just don’t have a good way of knowing who should get what drugs,” explains Gallagher. “Personalized care is going to help us with that through the use of biomarkers.”
But in developing targeted therapies and personalized medicine, Gallagher explains, we have to adopt a different view of cancer than the one that has guided most research to date.
“The real challenge,” Gallagher asserts, “is imagination.”
Traditionally, researchers have taken a reductionist approach to cancer study, focusing on one particular component of a cancer such as an enzyme or protein. But cancer operates in a robust and redundant way; if treatment blocks one mechanism by which it grows and spreads, it will often develop new ways of surviving. This renders the reductionist approach less effective.
“Our best way of understanding cancer is to understand the network as a whole and how it interacts,” says Gallagher.
This new approach would be informed by systems biology, the holistic study of interactions in biological systems. Researchers would look at the cancer in its entirety and at how the different processes influence each other, which Gallagher admits is extremely complicated—but feasible.
Despite his optimism about these promising developments, Dr. Gallagher is always mindful of the great challenges that cancer presents.
“My prediction is that the progress is going to be a lot slower than we think it might be,” Gallagher cautions. “I think that we’re going to find more and more levels of complexity. I think we’re going to have incremental improvements.”
Although Gallagher expresses reservations about finding a cancer “cure” anytime soon, he is hopeful that cancer will soon be seen as a chronic disease that patients can live with and manage.
“It’s not likely that we’re going to completely eradicate cancer when it is so robust, with all its redundant pathways,” he says. “It is much more likely that over time we’re going to learn how to manage this, much as we would manage heart disease and diabetes.”
For example, the targeted therapy imatinib (Gleevec), which works on the enzyme involved in gastrointestinal stromal (GIST) tumors, has made this rare cancer manageable. A growing population now lives with the cancer under control.
“I think all of cancer is going to be in that category,” Gallagher predicts. He says it may take years before patients—as well as doctors—are able to view cancer in this way and reduce the crippling fear associated with the disease.
“We’re stuck with a paradigm,” Gallagher muses. “If the facts on the table indicate that it’s not the right paradigm, yet this has been a ‘sticky’ idea—it’s been around for a long time—how do we change that? That’s a real obstacle: We have common ways of thinking that have been with us for decades, and we’re not likely to give them up immediately. And yet I believe that with all these innovations and discoveries, we should be looking at cancer in a totally different way.”
From global politics to business to journalism and entertainment, our rapid progress in knowledge and technology means that we’ll soon be looking at many fields in a totally different way.
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