NCI Objectives

It has become clear that cancer is a set of diseases that result from changes in the genome and the expressed products of the genome. These changes alter the structure, physiology, and genetic and chromosomal stability of the affected cells, and stimulate changes in the local microenvironment. The path of scientific opportunity resulting from this fundamental observation can have a profound impact on the management and prevention of cancer.

Currently, the diagnosis of cancer usually follows detection of a palpable tumor mass or a significant mass resolvable by anatomical imaging. The detection and diagnosis of the tumor is frequently many years after the earliest stages of cancer development. We know that early detection improves the outlook for success in patient treatment, and yet we are extremely limited in our capabilities to identify the earliest stages of cancer as they emerge. Diagnosis is most frequently accomplished through physical removal of a portion of the mass from the patient and pathological characterization. Significant strides have been made in minimizing the discomfort to the patient and risk of enabling the spread of the disease in this process, yet the process remains daunting for the patient. More critically, current pathological classifications do not provide adequate discrimination between diseases or prediction of outcome and response to therapy. Given the current mode where disease is detected at a relatively late stage and diagnosis is inadequately informative, therapy has largely been restricted to surgical removal, elimination through radiation, or relatively non-selective cytotoxic drugs with substantial side effects. Given the complexity of current strategies our ability to help those without direct access to sophisticated medical infrastructure is extremely limited. While we have had noteworthy success in curing certain cancers and alleviating symptoms for many patients, we wish to have better tools for treating all cancers and strive to eliminate the devastating impact in reduction of patient quality of life associated with current approaches.

The recognition of the molecular basis of cancers unveils a path of opportunity to create a future where cancers are detected, diagnosed, and treated based on the fundamental changes in the specific disease. The NCI is currently investing in the biological discovery that will enable that future. Current programs target the definition of the expressed gene products of the human genome, the identification of mutations and polymorphisms in genes critical to the development of cancer, discovery of sentinel biomarkers of the early presence of disease, and establishment of informative diagnostic classification systems based on the fundamental molecular changes in the individual diseases called cancer. Closely linked to these programs will be emerging programs to discover and exploit molecular targets for cancer prevention and treatment. Expanded investments in information analysis approaches and tools to apply to the data forthcoming from these biological discovery programs will reveal not only the signatures of interest, but also insight in to the underlying biological basis of the diseases.

The identification of molecular signatures of cancers will enable identification and diagnosis of potentially dangerous cells at an earlier stage than current anatomical detection allows. De novo identification of the minimal set of cells that carry this critical profile at the earliest point in the progression towards cancer could allow for interventions geared toward eliminating or preventing expansion of this population of cells and preventing the development of significant tumor burden and the need for radically invasive treatments, such as surgery. Similarly, knowledge of the signatures in resected or treated tumors could assist in detecting the presence of residual cells, metastatic foci, and the earliest signs of recurrence of disease.

How do we achieve this goal? Realization of this scenario would only be possible if technologies exist that allow us to identify profiles of early cancers and precancers in minimal numbers of cells in the living body. To achieve this aim requires dramatically new technologies to scan the body for the earliest signatures of emerging disease and support immediate, specific intervention. The ability to scan the body for early signatures requires these technologies to be minimally invasive. To prevent the rapid expansion of the disease and maximize the benefit of the earliest detection, future technologies should support the seamless interface between detection, diagnosis and intervention. Essential to the utility of these technologies is the development of information infrastructure and analysis tools that will link the information on basic discoveries, intervention discoveries, and clinical outcome information to specific patient histories to aid the care giver in making rapid, informed decisions about appropriate intervention.

What technological breakthroughs will take us to this future? Will the successful technology platforms be nanoexplorers in the living body, smart chemistries coupled with smaller, more effective imaging tools, or totally unforeseen innovations? It is likely that multiple approaches may be successful in meeting our goal. Rapidly emerging discoveries in the fields of nanoscience, chemistry, photonics, computational sciences, and information science and technology are likely to be key. While the path to success is not clear at this point, it is clear that with the development of minimally invasive technologies to support earliest detection, immediate diagnosis and response, comes the possibility to move from the treatment of symptomatic cancers toward the treatment of precancers and the elimination of the symptomatic diseases we describe today as cancer.