The Institute for Systems Biology, Caltech and the University of California Los Angeles have recently established a NanoSystems Biology Alliance (NSBA). The goals of the Alliance are to attack challenges in cancer and immunology and ultra-rapid disease diagnostics by integrating newly developed nanotechnology and microfluidics tools with modern cancer biology and immunology.

Modern science has generated a picture of cancer that has at its foundation specific molecular errors that instruct healthy cells to become those of disease. Virtually all cancers arise from a series of DNA mutations (errors) that accumulate in a single cell. One error may be genetically passed from parent to child, while others arise from external sources, such as environmental toxins, smoking, viruses or simply from mistakes in DNA repair that occur with aging. Consider a patient diagnosed today with breast cancer. A molecular-based analysis of that same patient might be “breast cancer type 32 resulting from mutations in the Her2 oncogene and the PTEN tumor suppressor gene.”

In other words, different breast cancer patients may have common clinical presentations, but different diseases. Thus, clinically treating breast cancer as a single disease is incorrect. The development and testing of new cancer drugs is similarly misguided without an informed diagnosis --the molecular description of the malignant cells and identification of vulnerable therapeutic DNA, RNA and protein targets. As a result, non-specific chemotherapy drugs (i.e. cis-Plat) or radiation are still the primary weapons used by oncologists, even after a 32 year-old and very expensive war on cancer.

Why, then, are breast cancers, prostate cancers, etc., all treated as single diseases?

Cancer diagnostic tools (mammograms, CT, MRI imaging, etc.) are based on identifying disease lesions (i.e. tumors), but not the molecular causes. PET molecular imaging can examine the molecular basis of disease in patients, but it needs guidance that establishes the molecular diagnostic criteria. An informative diagnostic description of disease requires the means to examine hundreds to thousands of molecular species – a concept beyond the scope of current clinical practice. Modern systems biology techniques (the coordinated measurement of the molecular signatures of genes and proteins that are the biological language of health and disease) provide a foundation for such measurements. Unfortunately, those techniques now require a large surgical tissue sample, are costly, are limited in the diversity of molecular species that can be examined, and are tedious. Thus, a combination of inadequate knowledge, antiquated clinical practices and inefficiencies in current tools of molecular diagnostics has kept an informed molecular diagnosis of disease – and from this the development of effective molecular therapeutics – a dream, rather than a reality.

This picture is changing, and a new wave of nanotechnologies are being developed that will revolutionize virtually every aspect of medicine – cancer is just one example. Imagine that a full molecular-based cancer diagnosis could be accomplished using just a few cells, at low cost, within seconds. With a drop of blood or with a low risk outpatient biopsy procedure, a cancer patient could be correctly diagnosed, even in the very early stages of the disease, within minutes. This would revolutionize drug discovery and clinical treatment:

• First, it would allow for the identification of the combinations of molecular errors that result in the various cancers;
• Second, it would hasten the development of drugs targeted to the critical and vulnerable molecular errors causing the cancer;
• Third, clinical trials to test those drugs, by targeting the appropriate patient pool, could be completed with smaller numbers of patients and lead to rapid approval by the FDA.
  
  The goal of the Nanosystems Biology Alliance is to make this vision a reality.