Wednesday, January 18, 2006

The Cancer Genome Atlas

The recent article here on current research into cancer noted in passing a new initiative of the NIH to produce an atlas of the whole "cancer genome".

NIH Launches Effort to Explore Cancer Genomics
The National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both part of the National Institutes of Health (NIH), today launched a comprehensive effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, especially large-scale genome sequencing. The overall effort, called The Cancer Genome Atlas (TCGA), will begin with a pilot project to determine the feasibility of a full-scale effort to systematically explore the universe of genomic changes involved in all types of human cancer.

Although the focus of the project is on cancer, it is actually much more ambitious than the original Human Genome Project, because cancer actually represents at least 200 distinct diseases, and the individual cells within a single tumor can have a variety of different mutations in their genes.
Cancer is now understood to include more than 200 different diseases. In all forms of cancer, genomic changes -- often specific to a particular type or stage of cancer -- cause disruptions within cellular pathways that result in uncontrolled cell growth. TCGA will delve more deeply into the genetic origins leading to this complex set of diseases, and, in doing so, will create new discoveries and tools that will provide the basis for a new generation of cancer therapies, diagnostics, and preventive strategies.

What this means is that the DNA of many individual cells will need to be sequenced. However, the problem can be somewhat simplified by being selective about what genes will be sequenced. In addition, the pilot phase of the project will concentrate on a limited number of types of cancer. Since a common characteristic of most cancers is that some normal DNA repair functions are disabled, the genome of a cancer cell is said to be "unstable", and gene mutations may accumulate rapidly. The pilot phase will therefore search for types of cancer that have the least amount of variability in its cells.

Although the task of building The Cancer Genome Atlas is daunting, one has to recall the experience of the original Human Genome Project. That project was completed sooner than expected and at less expense, because the technology of DNA sequencing advanced much more rapidly than expected. This occurred in large part because of the entry by J. Craig Venter's Celera Genomics with a parallel project to sequence the genome, in competition with the government's original project. There's no reason to think that sequencing technologies can't continue to improve rapidly to cope with the complexity of the task.

The ultimate rationale for the project, of course, is the hope that by knowing as much as possible about the kinds of genetic abnormalities which lead to cancer it will be possible to compensate for or counteract these abnormalities. Already the knowledge in a few cases of how particular cancers develop has made it possible to create drugs which interfere with the effects of the abnormalities, and thereby halt or even reverse the progress of the cancer. For example:
Genetic mutations linked to breast cancer, colon cancer, melanoma, and other cancers already have led to diagnostic tests that can point to the most effective intervention. Recent discoveries in cancer genomics have helped to identify several treatments that work by targeting cancer cells with a specific genetic change, such as GleevecĀ®, a drug for chronic myeloid leukemia and gastrointestinal stromal tumors, and HerceptinĀ®, a drug for one form of breast cancer.
Take CML as an example. It involves a fairly dramatic defect in which parts of two genes from separate chromosomes become combined, and the gene that results produces a hybrid protein (called bcr-abl) which is a very active "tyrosine kinase". That's a type of enzyme which acts on cellular receptor proteins to promote cell division, and the resulting excessive cell division yields CML. Gleevec, which has the scientific name imatinib, is a molecule which binds to the bcr-abl protein and blocks its kinase activity. It turns out that imatinib does not interfere harmfully with normal tyrosine kinases, and so it has no detrimental effects on noncancerous cells lacking the abnormal bcr-abl protein.


Additional links on the Cancer Genome Atlas:

The Cancer Genome Atlas - project home page

NIH Launches Cancer Genome Project - Washington Post

New Genome Project to Focus on Genetic Links in Cancers - New York Times


Tags: , , ,


Links to this post:

Create a Link


Post a Comment

<< Home