The concern about whether President Reagan's cancer has spread to other parts of his body is the same worry that plagues almost every cancer patient and physician.
"No one dies of primary breast or colon cancer tumors," says Jeffrey Schlom, who heads the National Cancer Institute's laboratory of tumor immunology and biology. "The question is when and where it will spread."
To date, cancer specialists have often been like an imperialist power waging a losing war against guerrillas. If they didn't quell the initial uprising early, odds were that the cancer troops would metastasize, or spread, to the farthest reaches of the body and ultimately kill the patient.
But today, some promising -- albeit often experimental -- techniques are beginning to tackle the problem. From new blood tests that can signal an early recurrence of colon, breast or ovarian cancer to the discovery of a hormone that seems to alter the growth of lung cancer, these emerging therapies offer help and hope for many cancer patients.
At the top of the list are monoclonal antibodies, chemical substances that allow physicians "to literally pick out a needle in a haystack," says Schlom.
Monoclonal antibodies are cancer detectives that can search out malignant cells. They are produced by the marriage of medicine and molecular genetics. In the laboratory, scientists fuse two types of cells -- one a cancer cell, the other a white blood cell -- into a special cell type called a hybridoma. This cell is then cloned and allowed to produce large amounts of antibodies known as monoclonal antibodies, which are tailor-made to identify a specific cancer cell type.
Experiments show monoclonal antibodies are particularly promising for detecting the spread of epithelial cancers -- the types of cancers that affect the breast, colon and ovaries. "We can isolate one in a million cells and grow the antibody to identify them in unlimited quantities," Schlom says.
Once the antibodies are manufactured, they are marked with radioisotopes, injected into patients and then monitored via a special gamma camera from one to six days later. The time lapse allows the antibodies to move through the blood and seek out tumors in various organs. If there are tumors, they show up on the scans as dark masses, providing an excellent roadmap for the surgeon.
When removed, the tumors are weighed and placed in a gamma counter to determine exactly how many radio-labeled antibodies they took up. This gives researchers like Schlom a window not just on tumor location but also on metabolism, giving them clues on how to stop the growth.
Today, monoclonal antibodies function as signposts in experiments to detect colon cancer and similarly pinpoint hidden tumor spread in ovarian and breast cancers. But within the next year or two, these microscopic detectives are expected to be used in treating cancer as well. By attaching cancer-fighting drugs to monoclonal antibodies, researchers expect to send lethal doses of drugs directly to cancer cells, leaving normal cells untouched. The idea, Schlom says, "is like using the same missile with a different warhead to fight the tumor."
Monoclonal antibodies also are being coupled with new blood tests designed to detect an early flare-up of cancer and are expected to improve upon the most widely used blood test, one that measures CEA, or carcinogenic embryonic antigen. Scientists believe that certain cancer cells produce CEA. As levels of CEA rise in the blood, the chance of cancer recurrence increases.
This is the test that President Reagan's doctors have recommended for frequent monitoring of his physical status. CEA levels are used as an early warning system for the return of colon cancer and, less often, to monitor the progress of breast and ovarian cancer patients.
But the drawback of CEA testing is that it seems to be accurate in only about seven of every 10 cancer patients, and actually finds elevated levels in about 5 percent of the population without cancer, reports Dr. Hilary Koprowski, director of the Wistar Institute in Philadephia. The reason for this is unknown. Several experimental tests are under investigation as potential complementary aids to CEA.
"I envision a cocktail of five or more blood tests for cancer patients," says Schlom. "That's where we're going. The state of the art may be very different in two years."
Another weapon moving into the anticancer arsenal is a substance known as interleukin-2. Found naturally in the body, and now produced in the laboratory by genetic engineering, interleukin seems to be a key component in a type of white blood cell recently identified by Dr. Steven A. Rosenberg -- one of President Reagan's doctors -- and his colleagues at the National Cancer Institute (NCI).
White blood cells, part of the immune system, are removed from the bodies of experimental animals and humans with cancer for treatment with interleukin-2. The treated cells are then returned to the body. In these studies, the technique proved effective in fighting lung and liver tumors, reducing their size.
Lung cancer remains one of the deadliest of all cancers. Even with the best available treatment, only 12 of every 100 patients with this disease in the United States achieve "long-term survival" of five years or more NCI reports.
Part of the difficulty in battling lung cancer has been both the many different cell types of lung cancer and the difficulty of growing lung cancer cells in the laboratory for further study. Both problems are being tackled by Dr. John Minna and his colleagues at NCI. Nearly 100 lung cancer cell lines have now been identified. And with the discovery of key growth factors, hormones crucial for the cancer cell's survival, researchers can now culture lung cancer cells in the laboratory and determine what drugs are most effective in a particular case.
Perhaps most promising is the work Minna presented at last year's annual meeting of the American Association for Cancer Research. One type of small cell lung cancer produces a hormone called bombesin, Minna reported. By controlling bombesin levels, the researchers found that they could manipulate lung cancer growth in animals. Clinical trials are now under way in lung cancer patients at NCI and the National Naval Medical Center in Bethesda.
Great inroads also are being made with interferon. Some 10 years ago, interferon was a media star, a hot new substance touted prematurely as the potential wonder drug for cancer.
Now after a decade of careful scientific research, interferon -- which scientists say "interferes" with cancer cell growth, although they don't know how -- is again moving to the forefront as a promising treatment not for all cancers, but for a select few.
Good results have been achieved against slow-growing lymphomas -- cancers of lymph nodes -- the type that prompted former senator Paul Tsongas (D-Mass.) to retire early from politics. Studies also suggest that interferon is as effective as some drugs now being used in treating cancer of the kidney, melanoma (a deadly skin cancer) and Kaposi's sarcoma, one of the diseases associated with acquired immune deficiency syndrome (AIDS).
But the best news about interferon, says the University of Michigan's Dr. Kenneth Foon, is its effectiveness in treating hairy cell leukemia -- a disease that afflicts about 3,000 to 4,000 Americans each year.
Unchecked, hairy cell leukemia replaces healthy bone marrow cells with malignant cells, eventually causing death. But clinical studies at several major medical centers, including NCI and M.D. Anderson Hospital in Houston, have shown that interferon can dramatically reverse the disease.
"Every time I see a hairy cell leukemia patient, I have a big grin because I know that I can take their disease and turn it around," says Foon.
"What's nice about cancer research today," says NCI's Schlom, "is that we know just what we have to do and we have the ability to do it."