Email this pageHow it All Comes Together
By establishing the "Signatures of Cancer" as a major priority area six years ago, NCI recognized that we had reached an important juncture in cancer research. Sophisticated, new molecular biology tools had allowed us to gather critical information about the molecular nature of cancer. Through these studies, we learned that cells have their own fingerprints, known as molecular signatures. A molecular signature, whether an expressed gene or a protein produced by the cell, is a unique biological characteristic that is related to a cell's function in the body. As a cell transforms from normal to premalignant to malignant, its signature changes and this change becomes a signal of the presence of cancer.
With this knowledge, we knew that molecular signatures research presented us with an "extraordinary opportunity" to revolutionize cancer detection and diagnosis. If we could accurately "read" the signature changes that distinguish a cancer cell from its normal counterpart, we could detect the changes that signal cancer at its earliest stage - perhaps even in its premalignant stage - as well as more accurately diagnose a tumor according to its molecular features and select appropriate treatments.
NCI established the signatures of cancer cells as an "avenue of discovery with the potential to change the face of cancer research and care." Every effort was made to focus resources needed to rapidly discover the molecular changes associated with all tumor cells, develop new technologies that visualize these changes, and deliver innovative approaches for early detection and diagnosis to the clinic. Through six years of intensive work, scientists inside NCI and throughout the country have made dramatic progress.
As a first step, NCI collaborated with several Federal and industry partners to launch the Cancer Genome Anatomy Project (CGAP) in 1997. The initial goal for this project was to establish a complete index of all expressed genes for normal, premalignant, and malignant cells. Today, having identified over a million genes in more than 40 tissues, NCI scientists are nearing completion of this ambitious original goal. And CGAP's goal has now broadened beyond developing the complete tumor gene index to uncovering all of the molecular information in a cancer cell and its components, including proteins.
Toward this goal, CGAP scientists are successfully building on the index by annotating the types of cells and cancers that express these genes, developing catalogues of chromosomal changes in cancer, and identifying common genetic variations among people that influence risk for cancer. All of this information is being used to build coordinated databases that will seamlessly construct - in seconds - a complete molecular picture of a particular cancer, providing a researcher who has discovered a questionable gene in a patient's tissue with information about its corresponding protein, the protein's function, and whether data suggests that the protein is a good target for treatment intervention.
CGAP's evolving data about the molecular changes associated with cancer continues to generate a goldmine of potential markers for cancer. In 1999, NCI moved to capitalize on this data by creating a new national resource, the Early Detection Research Network (EDRN). This partnership between NCI, other government agencies, industry, and academia takes advantage of a novel and complex research structure that enables scientists to rapidly discover, develop, and clinically validate risk and early detection markers.
Identifying these markers can be particularly challenging because they must be detectable at the very earliest stages of development. For this reason, EDRN scientists face the challenge of developing tests that are clinically adaptable, minimally invasive, highly sensitive and specific, and capable of identifying a few abnormal cells among billions of normal cells. To address these unique testing requirements, EDRN researchers work in separate yet coordinated development, validation, and clinical laboratories. This comprehensive, collaborative approach blends genomics and proteomics, providing a systematic and comprehensive view of how the molecular signatures of specific cancers can be used as unique identifying markers.
EDRN researchers already have successfully discovered a number of early detection biomarkers of several types of cancers, including breast, prostate, colon, and lung. For example, researchers are exploring the possibility that a distinctive protein profile found in nipple fluid taken from breast cancer patients may prove to be a useful early detection marker. In addition, NCI and EDRN scientists have applied proteomics in the development of a promising early detection test for ovarian cancer.
Our new, molecularly-based understanding of cancer has also opened new avenues to diagnosis. We can now move toward diagnosing and classifying tumors according to their molecular features rather than their appearance under a microscope. To build on this opportunity, NCI established the Director's Challenge: Toward a Molecular Classification of Tumors in 1999 to support the development of profiles of molecular changes in human tumors. Generated using genetic and protein-based strategies that can complement our current tumor classifications, these profiles will help clinicians select more effective treatments as well as reveal changes in tumor cells that can be tested as potential new therapeutic targets.
Already, results from these studies suggest that cancers previously diagnosed as the same are actually multiple, molecularly-distinct diseases. For example, molecular profile studies have demonstrated that diffuse large cell lymphoma is actually at least two different diseases, one of which is almost always cured by current therapy, and the other almost never cured with current treatment. This program is dramatically accelerating our efforts to accurately classify and effectively diagnose human tumors.
Our ultimate goal in all of these initiatives is to improve patient care. Therefore, it is critical that we translate all gains made through basic research studies on molecular signatures into clinical practices that benefit those at risk for cancer and those struggling to overcome the disease. NCI's Program for the Assessment of Clinical Cancer Tests (PAACT) is a translational program designed to ensure that new knowledge about cancer and new technologies are brought into clinical practice effectively. For example, a new PAACT initiative is providing support to scientists conducting clinical trials to evaluate a new classification scheme for a type of skin cancer.
As is often the case in science, our current achievements point to new avenues of discovery. The considerable progress that we have made in the area of cancer signatures has revealed that studies of the cancer cell alone are important but not sufficient to fully understand cancer development and progression. We now know that a cancer cell's interaction with cells within its microenvironment enables and encourages cancer growth. In light of this information, we not only are continuing our efforts to create a complete profile of the changes that occur in the cancer cell but also are broadening our focus to identify the signatures of normal cells in the microenvironment along with the signatures that reflect changes occurring as cancer cells interact with the host environment.