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Even Less-Specific Biomarkers May Be Useful In Cancer Battle

BioWorld Today Science Editor

Biomarkers remain one of the big themes at the American Association for Cancer Research annual meeting this week in Washington. Data released over the weekend showed that in the BATTLE lung cancer trial, cancers at the same stage and with the same histopathological features could nevertheless have molecular signatures that rendered them more or less responsive to treatments.

And Amgen Inc. garnered attention with its studies using next-generation sequencing to identify other genes besides K-RAS that can predict the response to panitumumab (Vectibix).

The BATTLE and Amgen studies are probably the prototype of the future of biomarkers as most people imagine it – and indeed, as it is ultimately likely to have the highest impact: Highly specific sequence information that can be used to prescribe equally specific drugs.

But at a press conference on Sunday dedicated to "A Multidisciplinary Approach to Cancer Detection and Treatment: What's on the Horizon," researchers also reported on less-specific biomarkers that can nevertheless give useful information.

One such example is the identification of circulating tumor cells, whose uses were described by Sunitha Nagrath, instructor of surgery and bioengineering at Harvard Medical School and Massachusetts General Hospital, at a press conference.

The ultimate goal of getting such cells also is to get tumor DNA sequence information from them. The advantage of using circulating tumor cells are that they could combine the specificity that can be gleaned from tumor DNA itself with the ease of a blood test. Circulating tumor cells "carry the signatures of the primary tumor, so they have a potential for prognosis and therapeutic purposes," Nagrath told reporters at a press conference on Sunday.

The disadvantage? "These cells are very rare – 1 in 1 billion," Nagrath said. "You need a very sensitive technology to isolate in sufficient quantity, and with sufficient purity, to do some downstream genotyping analysis."

In data published at the conference, Nagrath and her colleagues showed proof of principle that they were able to identify such circulating tumor cells, both in patients with advanced and with localized prostate cancers.

Nagrath and her colleagues used a so-called CTC-chip to isolate about 200 tumor cells from a teaspoonful of blood; she said that technology could use any surface marker antibody to trap the tumor cells, whose cancerous nature is confirmed by staining. The idea is similar to the approach pursued by San Jose, Calif.-based biotech Chronix Biomedical for both cancer and other diseases. (See BioWorld Today, March 9, 2010.)

In the advanced patients, Nagrath said, there was no correlation of circulating tumor cells with either serum PSA or tumor stage. But there was a "huge correlation" between circulating tumor cells and patient response that was "very helpful in monitoring response to the treatment." Responders were less likely to have circulating tumor cells, and fewer of the cells that the scientists did find were highly proliferative.

And even without specific sequence information, the mere presence of the cells might be able to give researchers valuable clues about the disease. In patients with early stage disease, Nagrath and her team were able to identify them in roughly 40 percent of patients.

Those patients are not expected to have any [circulating tumor cells] because by definition, they are localized. In some patients, "even after the surgery, there is a persistence of these circulating tumor cells . . . so what does that mean for the patients' prognosis? Are these patients then more likely to come back with recurrent disease? Are these indicators of more aggressive rather than indolent disease?" Nagrath and her colleagues are currently investigating those questions.

At the press conference, Nagrath said that circulating tumor cells could be used as a diagnostic alongside, or ultimately even replacing, prostate-specific antigen (PSA) as a diagnostic tool in prostate cancer.

Monday at the conference, PSA itself also got some attention, as researchers from Johns Hopkins University reported that by using the "prostate health index" – which combines measuring three different forms of PSA - they were able to predict which biopsies of men with early stage prostate cancer monitored by watchful waiting would show a clinical worsening. Currently, "there are no outward signs that these small prostate cancers may be progressing – men clinically feel the same and physicians are not likely to detect it on conventional imaging scans," presenter Robert Veltri, associate professor of urology and oncology at the Johns Hopkins Brady Urological Institute, said in a press release. "We believe that close monitoring with the right biomarker tools may help to detect this shift in pathological stage."

For additional coverage of AACR news, see AACR Roundup on pages 6 and 7.

Published: April 20, 2010