Yet among those with early-stage cancer, about half will experience a recurrence (relapse) following surgery because small, undetectable levels of it have spread to other areas (micro-metatastic cancer). This creates a dilemma for oncologists who must decide whether to recommend against post-surgical treatment, thereby running the risk that the cancer will return, or advising a patient to undergo unnecessary chemotherapy, thus erring on the side of caution. Just as half of those with early stage cancer will experience relapse, about half will either be over- or under-treated because there are no good methods for identifying who is (and is not) at high risk for relapse.
Serious ramifications stem from the decisions about post-surgical therapy. If a decision is made not to treat a patient who has potentially micro-metatastic disease, the opportunity to destroy the tumor in its early stage, when only a few tumor cells exist, is lost. When the cancer reaches detectable levels in these patients it is generally difficult to save their lives. Conversely, treating someone who is not at risk of relapse from micro-metatastic disease subjects him or her to the debilitating effects of chemotherapy. Depending upon the chemotherapy used, these patients are unnecessarily subjected to adverse long-term consequences such as mutated DNA, secondary cancers, and premature aging.
Can Apoptosis Proteins Predict Survival in Early Colon Cancer?
John Reed, MD, PhD, is the President and CEO of the Burnham Institute, La Jolla, CA, where he leads a team of some 40 researchers who are examining diagnostic testing methods aimed at pinpointing the likelihood of cancer relapse among patients with early-stage breast, colon or prostate cancer. Dr. Reed will present the status of their research during his presentation entitled, "Can Apoptosis Proteins Predict Survival in Early Colon Cancer?," at the 55th Annual Meeting of the American Association of Clinical Chemistry (AACC), being held July 20-24, 2003 at the Pennsylvania Convention Center, Philadelphia, PA. More than 16,000 attendees are expected.
Background and Research
When tumors arise, they often develop defects in the machinery that controls the lifespan and death of cells (the apoptosis machinery). These tumors also exhibit certain behaviors that make them resistant to cell death mechanisms. In the event a normal cell emanating from either the breast, color or prostate detaches, its epithelial cells will try, in a suspended state, to circulate in the blood or lymph and go elsewhere. These cells die, because their survival is dependent upon the signals they receive from their organ host. But if these cells have defects in their apoptosis machinery, they are able to survive despite being detached from their host organ, and survive in the circulating blood.
Understanding how apoptosis works is the focus of the Reed lab. He and his colleagues are researching antibody-based tests using immunological methods and apoptosis biology to examine the proteins encoded by various genes related to breast, prostate and colon cancer.
Specifically, they are applying immunodiagnostics to patient tumor specimens using archived materials. This retrospective approach allows them to correlate their results with the actual patient outcomes from samples provided nearly a decade ago. Based on the results, they have identified those that look promising and are now using them on other patient cohorts to ensure that the results are reproducible.
One cohort, for example, is comprised of 120 patients diagnosed with early stage II colon cancer which had been resected with margins free of tumors, had received no other therapy, and were clinically followed for eight years. Approximately half of these patients relapsed and eventually died. Their original tumors were obtained and have been used to conduct 50-60 different types of experimental tests. Of this large number of potential tests, four have been identified that, when used in certain combinations, predict with 98 percent accuracy who will relapse and who will not.
Next Steps
Confirmative studies on three cohorts are expected to be complete by the end of the year. Before physicians can utilize such tests, FDA approval is required. The Agency's approval will likely require a prospective study, with data obtained from patients deemed "relapse-free" for a period of five years. It is also common, however, for some specialty laboratories to make tests such as these available to some physicians to aid in clinical decision-making, recognizing that such use is only experimental. According to Reed, it is possible that within 18 months, if the confirmatory retrospective studies look promising, that some labs may be able to offer the tests on a non-approved basis.
Conclusions
The fruits of the genome, coupled with tests like those now being identified, mean that in the foreseeable future laboratories will be able to identify molecular and genetic signatures in cancers that will allow physicians to know which diseases are more aggressive and have acquired metatastic capabilities, and which tumors have not. This information will result in better clinical decisions about what the optimal therapies are for those diagnosed with early stage breast, colon and prostate cancer.
AACC Newsroom: July 20-July 24, 2003
Pennsylvania Convention Center
Room: 303B
Tel.:215-418-2429
The American Association for Clinical Chemistry (AACC) is the world's most prestigious professional association for clinical laboratorians, clinical and molecular pathologists, and others in related fields. AACC's members are specialists trained in the areas of laboratory testing, including genetic disorders, infectious diseases, tumor markers and DNA. Their primary professional commitment is utilizing tests to detect, treat and monitor disease.