Microbubbles and photoacoustic probes energize cancer researchers

The Canary Foundation’s eighth year of activities was marked with a symposium held at Stanford University May 25-27, 2010. The Canary Foundation focuses on the early detection of cancer, specifically lung, ovarian, pancreatic, and prostate cancer, in a three-step process of blood tests, imaging, and targeted treatment.

Imaging advances: microbubbles and photoacoustic probes
Imaging is an area that continues to make advances. One exciting development is the integration of multiple technologies, for example superimposing molecular information onto traditional CT scans. Contemporary scans may show that certain genes are over-expressed in the heart, for example, but obscure the specific nodule (tumor) location. Using integrins to bind to cancerous areas may allow their specific location to be detected (4 mm nodules now, and perhaps 2-3 mm nodules as scanning technologies continue to improve).

Other examples of integrated imaging technologies include microbubbles, which are gassy and can be detected with an ultrasound probe as they are triggered to vibrate. Similarly, photoacoustic probes use light to perturb cancerous tissue, and then sound detection tools transmit the vibrations. Smart probes are being explored to detect a variety of metaloproteases on the surface of cancer cells, breaking apart and entering cancer cells where they can be detected with an ultrasound probe.

Systems biology approaches to cancer
Similar to aging research, some of the most promising progress points in cancer research are due to a more systemic understanding of disease, and the increasing ability to use tools like gene expression analysis to trace processes across time. One example is being able to identify and model not just one, but whole collections of genes that may be expressed differentially in cancers, seeing that whole pathways are disrupted, and the downstream implications of this.

Cancer causality
Also as in aging research, the 'chicken or the egg' problem arises as multiple things that go wrong are identified, but which happens first, and causality, is still unknown. For example, in ovarian cancer, where there are often mutations in the p53 gene, and gene rearrangements and CNV (copy number variation; different numbers of copies of certain genes), but which occurs first and what causes both is unknown.

Predictive disease modeling
There continues to be a need for models that predict clinical outcome, and serve as accurate representations of disease. DNA and gene expression, integrated with traits and other phenotypic data in global coherent datasets could allow the ability to build probabilistic causal models of disease. It also may be appropriate to shift to physics/accelerator-type models to manage the scale of data now being generated and reviewed in biomedicine.

Gene Encyclopedia of all Life

A tremendous resource would be an open gene database of all of the genes present in eukaryotic, archaeal and bacterial life. There are several open genomic databases now but the information is organized around genomes and organisms rather than specific genes and gene function.

A gene database of all life is in the same vein as E.O. Wilson’s Encyclopedia of Life, but at the next level of detail. The Encyclopedia of Life hopes to provide a webpage with scientific information for every known species on Earth. The gene database would provide a webpage and scientific details for each gene present in life and include other information such as a cross reference to all of the different species in which the gene is expressed.

Merge the Entrez Genome Project and the PartsRegistry
The foundations and perhaps the vision and obviousness of a gene database of all life exist but not its targeted pursuit as a funded research priority. Existing genomics databases such as the U.S. NCBI’s Entrez Genome Project database could be extended and merged into one database that is more explicitly searchable by gene function, possibly joining forces with the PartsRegistry from synthetic biology which provides a homepage, datasheet and genomic sequence by gene or biological function.

NCBI’s Entrez Genome Project database genomic catalog of all life

Unifying the work of E.O. Wilson, Craig Venter, Penny Boston and Drew Endy
An interesting project would be the unification of the Encyclopedia of Life, genomics-by-organism databases and parts registry-by-gene databases together with the aggressive pursuit of cataloguing and sequencing newly discovered organisms and genes. A gene encyclopedia could rapidly extend human knowledge and facilitate the era of personalized medicine as these novel genes could have extensive application in human therapies and pharmaceuticals, energy, climate management, agriculture and other areas.

Tremendous novelty and diversity remains unstudied with species (E.O. Wilson), with organisms in the sea (Craig Venter), and with extremophile life in caves (Penny Boston); 70-90% novel organisms, most of which have not had any gene identification and sequencing, functional assessment and cataloging.

A data resource like a gene encyclopedia could also uplevel the research focus to analytics. It will be interesting to see if an era of fully fungible genes across life arises, how easy it is to transplant function and how function expresses differently in different life forms.