Johns Hopkins Gazette: May 12, 1997

Catching Cancer

Third in a Series

Mike Field
Staff Writer

Twenty-five years ago, when Richard Nixon declared the "War on Cancer" and Congress passed the National Cancer Act, optimism ran high. Although cancer was a large and growing cause of death across all sectors of American society, U.S. scientific knowledge and technological prowess was ascendant; less than 10 years earlier another president had promised the moon and American science had delivered. Before that, a group of scientists working around the clock had needed less than three years to invent the atom bomb.

Many felt that, given sufficient resources, science and technology would triumph again. Some even made bold predictions as to when cancer would be cured. Few, if any, imagined a scientific effort stretching forward into the next millennium.

Yet as the year 2000 approaches, the battle against cancer-- some have called it only a skirmish--continues. Tens of billions of dollars have been spent and several billions more in expenditures are projected. Although some notable advances have been made--particularly in the fast-growing childhood cancers and cancers of the blood--it has only been within the last five years that cancer rates in general have begun to decline after decades of consistent increase.

Although researchers have made tremendous strides in their understanding of how cancer occurs and develops, they have gained greater understanding of the great complexity of the disease. The word cancer refers to more than 100 distinct diseases manifesting themselves in different ways in different parts of the body. Few researchers believe anymore that a single "silver bullet" drug or therapy will be discovered that will treat them all. Most have come to acknowledge that many cancers, in their advanced stages, may be virtually impossible to cure.

This realization is compounded by the fact that a significant factor in the reduction of cancer rates has been modifications in behaviors and risk factors, rather than improved treatments. Part of the reason fewer people are dying of certain cancers is that, in general, fewer people are contracting the disease to begin with. Says School of Medicine researcher David Sidransky, who is a specialist in head and neck surgery related to cancer: "Theoretically, we could dissolve the department of head and neck cancers if everyone would just stop smoking. These cancers are extremely rare when not associated with smoking; so there is a degree of personal responsibility associated with preventing these diseases."

The other part of the equation has to do with earlier detection of the disease. While advanced cancers have remained stubbornly resistant to most treatment, the same disease, at an earlier stage, will often respond quite well to drugs, radiation, surgery or a combination of each. Various forms of cancer screening--ranging from routine breast examination and mammograms for women, to tests for blood in urine and the stool--are now strongly recommended by the National Cancer Society. This is the area of cancer research that Sidransky, an associate professor of oncology and of otolaryngology/head and neck surgery, believes will blossom in the coming years.

"What you've had in the last 25 years of cancer research is something of a philosophical split, with much more money going to finding a cure for cancer than to simply finding cancer early," he says. "The overwhelming majority of our efforts have been aimed at discovering a cure for advanced cancer, predominantly aimed at big tumors."

Recently, thanks in part to pioneering research conducted in his own laboratory, Sidransky has begun to notice a subtle shift in priorities occurring. "More and more scientists are beginning to conclude that prevention and early detection will save a lot more lives, and that we have great opportunities if we put good science into early detection," he says. He points to changes within the National Cancer Institute as evidence of that shift.

"The whole area of prevention is being reorganized," Sidransky says. "There is a realization of the limitations of what we can do in our ability to cure advanced cancer."

Yet even with a heightened sense of importance surrounding early detection, the tools available to clinicians are still relatively primitive, largely relying on symptoms or visual signs such as tumors that appear as shadows in mammograms and chest x-rays, or visual traces of blood in the stool or in urine. Thirty years ago, for instance, then-Vice President Hubert Humphrey discovered blood in his urine, which is sometimes a warning sign of incipient bladder cancer.

Humphrey's doctors looked for tumors and performed tests for abnormal cells, but were unable to make a definitive finding of cancer. As a result, they decided to postpone aggressive cancer treatment until such a time--if ever--more definite evidence of cancer became available. Nine years later a diagnosis of bladder cancer was confirmed, and Humphrey underwent radiation therapy and radical surgery for the disease. By then the disease was too far advanced, however, and Humphrey eventually died when the cancer recurred.

Three decades after Humphrey's initial discovery of blood in his urine, doctors still have only limited means of detecting bladder and other cancers at an early stage, before tumors are clearly visible.

But thanks to significant advances in genetics, molecular biology and our understanding of how cancer progresses, it may soon be possible to detect cancer long before tumors are visible.

"Genetic changes are what drives the cancer process," Sidransky says. "Using these gene mutations as markers, we know occur, we believe it is possible to develop tests for early detection of primary cancers that are not yet visible by light microscopy."

Over the past five years, Sidransky and his team of researchers housed on the eighth floor of the Ross Building on the East Baltimore campus have been investigating ways of detecting cancer-indicating genetic abnormalities in blood, sputum, breast milk and other bodily fluids. "We think we can develop early diagnostic tests anywhere we can get a body fluid," he says. "That would cover about 95 percent of the common cancers."

This kind of testing is different than the genetic testing for BRCA1 and BRCA2 that indicates a genetic predisposition to breast cancer, or similar tests that have been developed for colon and other kinds of hereditary cancers. Although these tests are now available and have garnered considerable media attention, they are only effective in indicating a predisposition to the disease, primarily among those who have a family history of the illness. Because only about 10 percent of all cancers are inherited, these tests may have only limited usefulness and cannot, at present, indicate actual onset of the disease.

New types of DNA analysis, on the other hand, are capable of detecting tiny groups of mutated cells that have been shed from a cancerous site before that site may even be visible. Using a technique called polymerase chain reaction, a single strand of DNA can be copied millions of times, in numbers sufficient to test for abnormalities indicating cancer. This, and related technologies may hold the key to developing highly accurate and relatively inexpensive genetic cancer tests that would require only a drop or two of bodily fluids for each test.

Sidransky and his team have already developed one such test for the detection of bladder cancer from a urine specimen; it is now undergoing multi-institutional trials, and Sidransky expects the data from the study will be announced before year's end. Early, limited research into this method has proven extremely encouraging, and Sidransky's research is now being funded through grants from both the National Institutes of Health and OncorMed, a diagnostic subsidiary of Oncor Inc. By co-funding the research, the Gaithersburg, Maryland-based pharmaceutical company hopes one day to introduce a line of low-cost genetic cancer tests.

Three years ago, Sidransky obtained a frozen specimen of Humphrey's urine from 1967, along with a sample of the tumor subsequently removed with his bladder. Using molecular diagnostic techniques similar to ones he is developing in association with Oncor Inc., Sidransky and his team were able to demonstrate there was evidence of cancer in Humphrey's urine, nine years prior to the vice president's definitive diagnosis.

"If we could begin picking up cancers this far in advance there would be all kinds of options open for treatment," Sidransky says. "Chemotherapies devoted to preventing tumors from forming might be especially effective. Simple surgery to remove a few small tumors could replace radical surgery that often removes entire organs. If we find many of these cancers early enough, they're curable. We are talking about a whole shift in the paradigm of cancer treatment."

And, potentially, a significant increase in the number of lives saved each year by the early detection and prompt treatment.

"I remain quite optimistic that within five years, molecular detection--and strategies for staging and tailoring treatment approaches--will be part of a routine physical exam for most people in the U.S.," Sidransky wrote in a September 1996 article in Scientific American. "The sensitivity of these tests may change our fundamental conception of cancer. Rather than becoming a frightful diagnosis linked to an inevitable tragedy, early-stage tumors will be caught and cured."

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