NCI's SPECS Program Explores Molecular Diagnostics in Cancer
A recent NCI Cancer Bulletin article described how Dr. Louis Staudt and his colleagues in NCI's Center for Cancer Research used molecular diagnostic techniques to differentiate Burkitt's lymphoma cells from those of diffuse large B-cell lymphoma. This new approach to the biology of cancer can be used to characterize the genes, proteins, and biochemical pathways within a cancer cell. Defining the genetic profiles of cancers through molecular diagnostics has been crucial in developing more effective cancer treatments.
NCI's Strategic Partnering to Evaluate Cancer Signatures (SPECS) program is exploring the potential of these technologies for improving cancer care. The program is examining genetic molecular profiles in different types of cancer and evaluating their application to specific patient populations to improve diagnosis, prognosis, and treatment. With first-year funding of $10 million, SPECS is supporting multidisciplinary research teams in community hospitals, national laboratories, and academic institutions in the United States, Canada, and Europe.
"Translational research to bring molecular profiling to the clinic is a complex undertaking," says Dr. James Jacobson, SPECS co-director and chief of the Diagnostic Biomarkers and Technology Branch in NCI's Division of Cancer Treatment and Diagnosis. "These studies involve scientists who understand the biology of molecular profiles, clinicians who treat patients, and large bioinformatics teams who analyze data from hundreds of patients.
"The use of microarray and proteomics technologies represent important advances in describing the genes that are altered in cancer," continues Dr. Jacobson. "Investigators have been able to classify tumors into subsets based on their molecular profiles, but we don't yet know if these classifications are relevant to important clinical questions. The goal of SPECS is to refine and validate these molecular signatures."
In SPECS, clinical need dictates which molecular profile will be evaluated. "NCI recently launched the TAILORx clinical trial to identify women who would and would not benefit from a particular chemotherapy regimen following breast cancer surgery," comments Dr. Jacobson. "SPECS is supporting the same type of research that led to the development of the test used to determine the appropriate therapy in TAILORx. In the next few years, we're hoping that SPECS research will lead to similar trials for other cancers."
SPECS supports six research teams, each studying a different cancer type: breast, prostate, and lung cancers; childhood sarcoma; acute leukemia; and non-Hodgkin lymphoma. Researchers will evaluate, refine, and validate previously identified molecular profiles for each cancer. The molecular profiles will include diagnostic profiles that characterize specific cancers; prognostic profiles that indicate the likelihood of patient survival, regardless of treatment; and predictive profiles that indicate an individual patient's response to a specific therapy.
Molecular profiles are also useful for prognosis. "Our laboratory studied the molecular profiles of mantle cell lymphoma and found that they could help determine the most effective treatment for these patients," comments Dr. Staudt. "Patients who had survived about 7 years after diagnosis had a molecular profile that was very different from the profiles of patients who had survived less than 1 year after diagnosis. These profiles could be used to identify patients with aggressive disease who need immediate chemotherapy."
SPECS is supporting Dr. Staudt's academic collaborators who continue to evaluate molecular profiles of non-Hodgkin lymphomas. "Over the next 3 years, we'll analyze the molecular profiles in 2,400 lymphoma samples," said Dr. Staudt. "We hope to develop a device to analyze the molecular profiles present in lymphomas that can be adapted to clinical use."
"Molecular profiles provide us with information about the many genetic changes occurring in a tumor," concludes Dr. Jacobson. "If a profile is associated with an unfavorable patient outcome, we can use aggressive therapy. The profile may also predict a patient's response to therapy. These are the insights that will lead to patient-tailored therapies in the future."
By Lynette Grouse
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