A cure for cancer: past failure, future hope

Childhood leukemia has yielded to treatment, but the treatment of many tumors of adults — of the lung, the pancreas, the liver or the brain — has not been as successful despite the resources that have been marshaled. A short column cannot explain the failures of the past, what we learned while failing or what the future might hold, but a recent book, “The Emperor of All Maladies — a Biography of Cancer,” by Dr. Siddartha Mukerjee (also of Columbia University), comes close. (Note: Dr. Mukerjee won the Pulitzer Prize for general nonfiction this week for this book.) Cancer has always been with us, but treatment did not become possible until anesthetics and aseptic techniques to control infection made surgery safer at the end of the 19th century. While life-saving operations surely occurred, drastic operations for breast cancer took away the breast, the lymph nodes, then all the chest muscles, thinking that would get all of the cancer cells. It was an illusion — cancer spreads to distant sites through the circulation. Women were unnecessarily mutilated for many decades.In the early 20th century, radiation was used to suppress the growth of tumors — it preferentially kills dividing cells such as those in tumors, but it is also indiscriminate and causes great collateral damage. Surgery and radiation, in more sophisticated forms, remain among the foundations of cancer therapy.Dr. Mukerjee’s book explains surgery, radiation and the origins of chemotherapeutic drugs. Who knew that the explosion of a ship carrying mustard gas in the harbor at Bari during the invasion of Italy led to chemotherapy? The hundreds of Allied soldiers who died had no functioning bone marrow and hence could not make white or red blood cells. After the war, oncologists realized that compounds like those in mustard gas could be used to inhibit the formation of leukemia cells in the bone marrow. Mustard gas derivatives are still used. Other drugs that inhibit DNA synthesis (and hence the cell division that lies behind the formation of tumors) were employed, initially at Boston Children’s Hospital under the direction of Dr. Sidney Farber. The drugs also stopped the growth of normal cells — hence the familiar loss of hair, the inhibition of blood formation and bad effects on the intestines where new cells are constantly replacing old ones. The new drugs delayed death for a while, but eventually the patients relapsed. The drugs failed, but raised the possibility that the disease could be treated. It would, people thought, be a question of combinations of drugs, ways to apply them and keeping patients alive while these noxious drugs worked to kill cancer cells. For leukemia this was true, but for most adult tumors there was limited success.In 1971 (we are almost exactly at the 40th anniversary), the nation was putting people on the moon and the technical expertise that went into it was inspiring. President Nixon, under political pressure, declared war on cancer — proper organization, he thought, would be just as effective as NASA had been. The difference was that we understood the physics of spaceflight — how much energy to get a spacecraft to the moon and back — but we did not understand what drove the division of cancer cells to form tumors. Promises to cure cancer by 1980 were doomed, although the money financed an immense amount of basic and clinical research.What has changed since 1970? There has been a revolution in molecular biology, in DNA manipulation and sequencing. Chemists can make hundreds of thousands of compounds to be tested on cancer cells, and the computer revolution has made it possible to keep track of all the results. We have got into the instruction manual of the cancer cell. We have learned what regulates cell division — not only the mechanical process, but what starts and stops it. We have realized that cancer is not one disease but many and therapy must be tailored to the properties of individual tumor types. Slowly, drugs like Herceptin for one form of breast cancer and Gleevec for a form of leukemia and certain intestinal cancers have become available, and more such drugs are in clinical trials. Unlike surgery, radiation and earlier forms of chemotherapy, the new drugs are specific for cancer cells.In a previous column, I asked Dr. John Truman how, in the 1960s, he could stand a 100 percent mortality rate among children he was treating for leukemia. He said that the history of medicine shows that when science and intelligence are applied to a problem, things get better. Given the failures of the last years, some people have questioned this confidence, but Dr. Truman is still right.Dr. Mukerjee’s book explains the road we have traveled, the mistakes we have made, and the politics behind cancer prevention, research and treatment. He is circumspect but hopeful about what may happen in the next decade. Interwoven with a deeply researched story is a personal one — the training of a young scientist physician and the experiences of some of his patients. I assigned the book to some of my students and their enthusiasm makes it easy to recommend to people who are neither scientists nor physicians. This is the second part of a series on cancer. Richard Kessin, Ph.D., is professor of pathology and cell biology at Columbia University. He and his wife, Galene, live in Norfolk.