Researchers at the University of Michigan, Johns Hopkins and the Institute of Bioinformatics in India have discovered a gene-expression "signature" common to distinct types of cancer, renewing hope that a universal treatment for the nation's second leading killer might be found.
Scientists essentially abandoned the search for a common approach to cancer therapy after research launched by the 1970s "War on Cancer" revealed the many varieties of cancer and the differences among even the same type of cancer in different people. As a result of these discoveries, the focus largely has been on tailoring treatments to specific forms of cancers and even to the precise biology of cancer in a particular person.
"Perhaps we'd learned so much about the differences among cancers that we stopped looking for the similarities. Not having the right tools to look for similarities on a global level didn't help, either," says Akhilesh Pandey, assistant professor of biological chemistry in the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins and chief scientific advisor and founder of the Institute of Bioinformatics, a nonprofit institute located in Bangalore, India.
In the team's hunt for an overall genetic signature of cancer, which could be useful for diagnosis as well as for developing therapies, the scientists mined a mind-boggling amount of raw information by first creating an online searchable database of 40 published data sets that had collectively analyzed the gene expression "fingerprints" of more than 3,700 cancer tissue samples.
Searching the collected data for common patterns of altered gene expression, the researchers uncovered a "signature" common to all cancers and another that distinguished some kinds of aggressive tumors from their less aggressive counterparts. Their report appears in the June 22 issue of the Proceedings of the National Academy of Sciences.
The signature consisted of 67 genes that were abnormally expressed in all cancers. These genes largely are involved in the cell's preparation for division -- called the cell cycle -- and cell proliferation, the researchers report. Since cancers are characterized by uncontrolled cell division, the discovery is logical, even though it wasn't easy, says Pandey.
"A lot of the available data on gene expression in cancers was just 'warehoused' -- it was there, but not connected to anything," he says. "We took that data, analyzed it and connected it to relevant information. Now it's both available and useful."
Pandey and staff at the Institute of Bioinformatics last year reported creation of the Human Protein Reference Database [http://www.hprd.org], an online, searchable, information-rich database of known human proteins and their interactions.
The new project, initiated by Arul Chinnaiyan, M.D., Ph.D., at Michigan, took a similar approach to the cancer problem by developing a way to statistically analyze microarray data and applying the new approach to data from microarray experiments on tumor samples.
Microarray experiments let researchers determine the expression of tens of thousands of genes all at once, providing a molecular "fingerprint" of the tissue sample. Scientists then compare the fingerprint of one sample to that of another -- a prostate tumor to normal prostate, or aggressive breast cancer to non-aggressive breast cancer -- to identify genes whose expression is higher or lower than "normal." The idea is that those genes may contribute to the two tissues' differences.