Molecular Diagnostics

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Slide on Machine

Molecular diagnostics is a new approach to understanding the biology of cancer.  It offers the ability to characterize the genes, proteins and biochemical pathways within a cancer cell. Using molecular diagnostics to define the genetic profiles of cancers has been a pivotal development in the delivery of more effective treatments for cancer. For some cancers, clinicians can select the most effective therapy based on the specific genes expressed in a patient’s tumor.

To explore the potential of these technologies for improving cancer care, the National Cancer Institute launched the Strategic Partnering to Evaluate Cancer Signatures (SPECS) program. This program will examine genetic molecular profiles in different types of cancer and evaluate the application of these profiles to specific patient populations to improve diagnosis, prognosis and treatment decisions.  SPECS will support multidisciplinary research teams working in community hospitals, national laboratories, and academic institutions in the United States, Canada and Europe.

“Conducting translational research to bring molecular profiling to the clinic is extremely complex,” said James Jacobson, Ph.D., co-director of SPECS and chief, 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 bioinformatic teams to analyze data obtained from hundreds of patients.”

Applying molecular genetic profiling to cancer is challenging. Although it is possible to identify a single gene that may signal a more aggressive type of cancer, multiple genes affect the development and progression of a normal cell to malignancy.  These genes are influenced by many factors from both inside and outside the cell.

The research projects supported by SPECS will build on earlier NCI programs that investigated the molecular characterization of human tumor specimens using microarray technology, a method that simultaneously measures the activity of many genes in a single sample. From this analysis, a specific set of genes or molecular profile — a description of the genes active in a cell — emerges that can provide far more specific and reliable information about a tumor.  However, key to using molecular profiles is determining which of the thousands of genes that are changed within a particular cancer are relevant to describe the tumor and to determine what treatment would be most effective. 

“Being able to use microarray technology was an important advance in describing the genes that are altered in cancer,” said Jacobson. “Investigators were able to classify tumors into subsets based on their molecular profiles, but it is unclear if these classifications are relevant to important clinical questions. For example, could the profiles indicate effective cancer treatments or survival for individual patients? Refining and validating molecular signatures is the goal of SPECS.”  
In SPECS, the clinical need will dictate what molecular profile will be evaluated. “Profiles that predict the risk of disease recurrence for early-stage breast cancer patients could be very different than the profiles that predict risk to develop metastatic disease for patients with advanced breast cancer,” explained Jacobson. “In addition, different gene profiles may indicate the most effective therapy for treating each type of breast cancer.” 

Six research teams are supported by SPECS, each studying a different cancer type. These cancers include breast, prostate, lung, childhood sarcoma, acute leukemia and non-Hodgkin’s lymphoma. Researchers will evaluate, refine and validate molecular profiles that have been previously identified for each cancer. The molecular profiles will include diagnostic profiles that more accurately characterize specific cancers, prognostic profiles that indicate the likelihood of patient survival, regardless of treatment, and predictive profiles that would indicate a patient’s response to a specific therapy. This research is supported by grants totaling $10 million for the first year of the SPECS program.

One of the projects supported by SPECS is the continuation of an earlier NCI program. This study applied microarray analysis to aid the diagnosis of non-Hodgkin’s lymphoma—a tumor of B-cell lymphocytes, a type of white blood cell.

Several lymphomas classified as non-Hodgkin’s can be difficult to diagnose using traditional methods. “Molecular profiles can be used to improve the diagnoses made by pathologists,” said Louis Staudt, M.D., Ph.D., chief, Lymphoid Malignancies Branch, in NCI’s Center for Cancer Research. “In the majority of cases, a clear diagnosis is easy to make. However, about five percent to 10 percent of tumors lack classic hallmarks of disease and can be confused with another tumor type, leading to an incorrect diagnosis. Using molecular profiles could help refine the diagnosis and provide the information needed to differentiate these different types of lymphoma.”

Molecular profiles are useful not only in diagnosis of cancer, but also for prognosis. “Our laboratory studied the molecular profiles of mantle cell lymphoma—a type of non-Hodgkin’s lymphoma affecting middle-aged and older adults— and found that profiles could aid in determining the most effective treatment strategy for these patients,” commented Staudt. “Patients who had survived about seven years after diagnosis had a molecular profile that was very different from the profile observed in patients who had survived less than one year after diagnosis. These different profiles could be used to identify patients with aggressive disease—who need immediate chemotherapy—from patients who do not.”

SPECS will support Dr. Staudt’s academic collaborators who continue to evaluate the molecular profiles of non-Hodgkin’s lymphomas. “We’ll analyze the molecular profiles in 2,400 lymphoma samples, prospectively, over the next three years,” said 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 more information about the many genetic changes occurring in a tumor,” concluded Jacobson. “If a profile is associated with an unfavorable patient outcome, we can intervene with aggressive therapy. The profile may also predict a patient’s response to therapy. These approaches are providing the insights that will lead to patient-tailored therapies in the future.”

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