When Will We Cure Cancer?

By Shannon Brownlee

Talk about wishful thinking. One might as well ask if there will be a war that will end all wars, or a pill that will make us all good looking. It is also a perfectly understandable question, given that half a million Americans will die this year of a disorder that is often discussed in terms that make it seem less like a disease than an implacable enemy. What tuberculosis was to the 19th century, cancer is to the 20th: an insidious, malevolent force that frightens people beyond all reason--far more than, say, diabetes or high blood pressure.

The problem is, the "cure" for cancer is not going to show up anytime soon--almost certainly not in the next decade. In fact, there may never be a single cure, one drug that will bring every cancer patient back to glowing good health, in part because every type of cancer, from brain to breast to bowel, is different.

Now for the good news: during the next 10 years, doctors will be given tools for detecting the earliest stages of many cancers--in some cases when they are only a few cells strong--and suppressing them before they have a chance to progress to malignancy. Beyond that, nobody can make predictions with any accuracy, but there is reason to hope that within the next 25 years new drugs will be able to ameliorate most if not all cancers and maybe even cure some of them. "We are in the midst of a complete and profound change in our development of cancer treatments," says Richard Klausner, director of the National Cancer Institute. The main upshot of this change is the sheer number of drugs in development--so many that they threaten to swamp clinical researchers' capacity to test them all.

This welcome boom in cancer drugs owes its beginnings to one of this century's greatest scientific insights: that cancer is caused not by depression or miasmas or sexual repression, as people at various times have believed, but by faulty genes. Every tumor begins with just one errant cell that has been unlucky enough to suffer at least two, but sometimes several, genetic mutations. Those mutations prod the cell into replicating wildly, allowing it to escape the control that genes normally maintain over the growth of new tissue.

This realization has transformed cancer, in little more than a decade, from an utterly mysterious disease into a disorder whose molecular machinery is largely understood. Now cancer biologists are in the midst of their second epiphany: the recognition that tumors evolve, in Darwinian fashion, as each succeeding generation of cancer cells accumulates genetic mutations. "Survival of the fittest applies to cancer cells," says Richard Schilsky, associate dean for clinical research at the University of Chicago. "We now think of cancer not as a disease but as a genetic process."

This new view has sparked innovations that will manage the process and keep it from killing large numbers of people. "We are going to see a real shift from diagnosis and treatment to prediction and prevention," declares California surgeon Susan Love, author of Dr. Susan Love's Breast Book. Indeed, if all goes well with current clinical trials, women at high risk for breast cancer will soon be able to be screened with a device that removes a sample of breast cells through the nipple. If any cells show signs of the early mutations that lead to cancer, doctors can suggest the drug tamoxifen, which is believed to reduce the risk of breast cancer by suppressing precancerous cells. Drugs with fewer side effects that can also prevent breast cancer are already in the pipeline.

Within five years, early detection will be available for many other types of cancer as well. A stool sample will be all that is needed to search for colon-cancer cells on their way to becoming tumors, and drugs like the new COX-2 inhibitors, which are improved versions of pain killers, can prevent those precancerous cells from progressing. By the end of the next decade, a simple blood test could alert doctors to a wide variety of cancer precursors.

Treatments for more advanced cancers, however, are farther over the horizon than anybody can see. What is clear is that oncologists must take a page from aids treatment and use a cocktail of drugs with very different modes of action to outsmart tumors that have already begun to spread or metastasize.

That's because a tumor is made up of a hodgepodge of cells containing different genetic mutations, each of which allows it to wreak a different brand of havoc. Some mutations spur rapid growth; others prod nearby blood vessels into sprouting new capillaries; still others send cancer cells out into the bloodstream, where they can seed new tumors. Within 10 years, predicts Robert Weinberg, a cancer biologist at the Whitehead Institute in Cambridge, Mass., "we will analyze the mutant genes and then tailor-make a treatment [for] that particular tumor."

One day there will be drugs to trip up a cell at each of the steps it takes on the path to malignancy. A patient with lung cancer, say, might undergo gene therapy, breathing in genetically altered cold viruses that don't cause infection but instead act as miniature delivery vans carrying copies of the p53 gene. Good copies of this gene, which is mutated in many cancers, can force some cancer cells to commit suicide. The effects of p53 could be bolstered with antibodies that slow tumors by attaching to the surface of cancer cells and gumming up their ability to take over the body's growth factors, the specialized proteins that promote cell reproduction.

If a tumor has acquired the mutations for spreading, the doctor of the future may call on matrix metaloproteinase inhibitors, a new kind of drug that can be taken orally to block the enzymes a tumor uses to break down the cells of surrounding tissue and invade it. Vaccines cobbled together from whole cancer cells or bits and pieces of those cells have been shown to boost the body's immune system, helping it recognize and kill tumors on its own. "This was all a dream five years ago," marvels John Minna, director of the Hamon Center for Therapeutic Oncology Research at the University of Texas Southwestern Medical Center in Dallas.

Also close to reality are the so-called antiangiogenic factors, relatively nontoxic compounds that inhibit the growth of new capillaries. The idea behind this new class of drugs is that tumors cannot grow bigger than a few hundred thousand cells--about the size of a peppercorn--without growing their own blood-supply system. Researchers and patients, not to mention the owners of stock in half a dozen biotech companies, are eagerly awaiting results of clinical trials of antiangiogenic factors, which might be used in combination with chemotherapy to knock down big tumors and then prevent any surviving tumors from growing enough to do further damage.

The assumption behind many of these futuristic scenarios is an idea that most researchers have begun to embrace but that many patients will undoubtedly find difficult to accept. That is the prediction that certain cancers may require treatment for the rest of a patient's long life. Coming out of a century that declared war on the disease, a century that felt the only reasonable response to a tumor was to annihilate it, this may be hard to imagine. But turning cancer into a controllable condition is not so different from treating high blood pressure or diabetes. "I don't think curing cancer is the goal," says Ellen Stovall, executive director of the National Coalition for Cancer Survivorship. Instead, she says, "it should be helping people live as long and as well as they can."

No, we probably won't cure all forms of cancer in the 21st century. But we may very well learn to live with them.

Science writer Shannon Brownlee's work has appeared in the New York Times, the New Republic and the Atlantic Monthly