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DNA Chips Prove Indispensable in Cancer Research -- AACR Meeting

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Proteomics may have been the word on everybody’s lips at the American Association for Cancer Research meeting earlier this month in San Francisco, but a quick glance at the papers presented reveals that DNA microarrays are the technology that nearly everyone in basic research has been carrying in their back pocket.

“Cancer has been one of those fields where microarray research has just exploded,” said Dennise Dalma, an Affymetrix scientist who attended the meeting. “The year before people were talking about what could be done with microarrays, and this year, people were actually presenting results of what happened when these arrays were used in cancer research.”

In fact, there are data to back up this claim: Olli Kallioniemi of the National Human Genome Research Institute has tracked the increase in microarray papers at AACR over the past several years, and has found a 3.5 fold increase every year. This year was no exception.” Last year, we had about 1,000 papers, this year we had over 3,000,” said Kallioniemi. “It’s like Moore’s law for computers, but more.”

Kallioniemi also went through the AACR program online and did keyword searches. He found that the three most common terms were apoptosis, breast cancer, and prostate cancer in that order, but the fourth most common word was microarray. “It’s clear that DNA microarray [experiments] are becoming a routine and necessary investigation in almost any aspect of basic cancer research,” he said.

While microarray technology seems to be flooding the field, other AACR attendees said the deluge does not seem to be letting up.

“My perception was that the DNA [array] field was becoming saturated,” said Robin Stears, chief microarray scientist at Telechem/ArrayIt. But she discovered at the conference that there are “a huge number of researchers just beginning to apply [microarray technology] in the cancer field.”

 

Motorola Gets More Than Static At Meeting

 

This continuing upward curve in microarray usage is good news for microarray manufacturers, especially Motorola, which faces an uphill battle in a field where Affymetrix has become almost synonymous with pre-fabricated arrays. “We met a lot of people who are interested in using microarrays, who are at the early stage of their use of arrays,” said Nancy Schmelkin, Motorola’s CodeLink product manager.

Schmelkin said Motorola is targeting its arrays to the needs of cancer researchers in two ways: by providing protocols that allow the researchers to use very small samples gleaned from biopsies, and also in tuning the system to be sensitive enough to detect changes in expression over a matter of several hours for time course studies. “We have some studies going on now that I believe are going to demonstrate our ability to do that.”

At the meeting, researchers from Mount Sinai School of Medicine presented a poster on research using Motorola CodeLink arrays to characterize liver cancer gene expression.

Affymetrix, meanwhile, has seen published cancer studies using its arrays proliferate. “A couple of months ago, there were 183 studies, now there are 300,” said Dalma.

 

Hello Proteomics Doesn’t Mean Goodbye DNA Arrays

 

Could proteomics snuff out this wildfire? Hardly anyone in the field seems to think so. Since proteomics technologies and DNA arrays “don’t measure the same thing, they are complementary,” said David Botstein, head of the genetics department at Stanford Medical School. Botstein dismissed the proteomics hubbub as the hype that accompanies any emerging technology, including the buzz about DNA arrays a couple of years ago.

Additionally, DNA arrays have a technological leg up on protein chips given that oligonucleotide probes can be synthesized for any sequence of DNA, while a unique antibody capture agent has to be designed for each target protein. “This is very rate-limiting,” said Dalma.

What participants do see, however, is the beginning of a trend to use microarrays along with other technologies to elucidate different pieces of the metabolic pathway puzzle in cancer. “All of these pathways are going to come together and give us a global view that allows us to treat people better [for cancer] and understand why certain drugs have different side effects,” Dalma said.

 

Next Stop: Clinical Trials?

 

Now that they are using arrays at the basic stage, researchers are mulling how they can effectively incorporate them in research further down the pike. “There’s a lot of discussion now of the integration of the molecular profiling of cancers directly into the clinical trial,” said Kallioniemi. “What would be done is to carry out the clinical study, then afterwards, molecularly profile the cancers that did respond to the therapy and compare those profiles to those that did not respond, then design a new trial or a new way of administering the therapy in a more targeted manner.”

David Beer, a University of Michigan researcher who presented research that used microarrays in stage-one lung adenocarcinomas, said he envisioned the use of microarrays not only as a method to determine who is likely to respond to a particular treatment, but also as a way to identify subgroups within a class of patients that might benefit from additional therapy.

In the meantime, he said, the array field has to move forward from the simple experiment comparing tumor cells to normal cells, to more complex designs with clinical relevance. “Right now I would say the array field is in a ‘let’s do the easy experiment first’ stage,” said Beer. “It’s a harder question to look for molecular profiles within one specific subclass of tumors. You have to have the right specifications and design the experiment in such a way that you are comparing apples to apples. But that is where people are going.”

— MMJ