Why has cancer been so difficult to cure?

In 1954, there was a horrendous polio epidemic. By 1958, almost no one got polio. The 1960s saw the end of measles, mumps and rubella. After 1945, antibiotics tamed previously frightening infections. The public got used to these victories and waited for cancer to be next. But cancer remained “The Emperor of All Maladies” — the title of a recent book by oncologist Siddartha Mukerjee. Despite a War on Cancer announced by President Nixon and the investment of vast resources, cancer remains. How is this possible? Paradoxically, it helps to start with one instance in which there has been success — childhood cancer. Dr. John Truman, professor emeritus of clinical pediatrics at Columbia University, is a Goshen resident whose career in pediatric oncology began 50 years ago when all children with leukemia died. (He has almost retired. Last week, to demonstrate pulmonary function, he played his bagpipes for the medical students at the College of Physicians and Surgeons.) It gives him pleasure to say that 90 percent of children with leukemia now survive, although the treatment is arduous. I asked him how, in the 1960s, he could stand what he called “the gut-wrenching tragedy of a fatal disease visited on an innocent child,” but he said that he long ago realized that the history of medicine shows that when science and intelligence are applied to a problem, things get better. It is a positive outlook that some people, seeing the problems of adult cancer treatment, have begun to question, but let’s leave adult cancer for the next column, when we will revisit Dr. Mukerjee’s book. Cancer is a disease of cell division. We arise from a fertilized egg and we end up as adults of trillions of cells, which means a lot of cell divisions. Cell division is a complex and choreographed process. Type “cell division” into Google and you will see what I mean. Cell division must also be regulated — turned on when you need white blood cells to fight an infection and turned off when you don’t. White blood cells have precursors in your bone marrow that divide actively, making a large population of disease fighting cells. Gradually these white blood cells, or leucocytes, acquire all of the molecules necessary to fight disease and then they stop dividing. Only then do they enter your circulation. If the precursors of white blood cells do not stop dividing, they do not acquire disease-fighting properties. These immature cells burst into your blood stream and create leukemia, which means white blood. According to Dr. Truman, who radiates good-natured authority, there are several reasons we are doing better with childhood leukemia than adult cancer. One is that children are more resilient than adults and better withstand the brutality of chemotherapy. Another is an insight that physicians at St. Jude’s hospital in Memphis had in the 1960s. They could wipe out leukemic cells in the bone marrow with various metabolic poisons, but the disease always came back — due to leukemia cells lurking in the central nervous system where the drugs do not penetrate. They added radiation to kill the cancer cells in the nervous system, which prolonged survival. Success with childhood leukemia is also due to a medical system that treats children and adults differently. Almost all children with leukemia are treated in academic medical centers. It does not matter whether a child has insurance — sChip or Medicaid or other resources cover the costs. All children are treated as part of a hematology service and almost all leukemia patients were (and are) part of clinical trials that include all of the United States, Canada and other countries. Different regimens of drugs and radiation or transplantation were tried so that gradually, oncologists, who were in close contact, boot strapped their way from complete lethality to a relatively high cure rate. No child ever got less than the best therapy known at the time. Dr. Truman pays tribute to the bravery of the young parents, who knowing that their child had a lethal disease, allowed them to be entered in these clinical trials.Adult cancers are treated in doctors’ private offices and relatively few patients are entered in clinical trials. Chemotherapy is well reimbursed, even when it is not very effective. To be fair, there is a greater variety of solid adult tumors than children’s tumors and they can be biologically very different, but there is a little doubt that the setting for treating childhood cancer had as much to do with success as did all the novel (and still noxious) drugs. Is there new hope for adult cancer? Yes, but do not expect a knockout punch. This is the first of a series of columns on cancer. Richard Kessin, Ph.D., is professor of pathology and cell biology at Columbia University. He and his wife, Galene, live in Norfolk. He can be reached at rhk2@columbia.edu.