Science Editor

Targeted cancer drugs have a lot of hope riding on them – both because of the potential rewards of developing them, and because of the risks of not doing so.

"A lot of drugs have not been approved because they have been tested in the wrong populations," leading to failed trials, Alessandra Cesano, chief medical officer and chief operating officer at Nodality Inc., told BioWorld Insight.

And researchers' ability to find the molecular snafus that underlie cancer has far outstripped their ability to find which patient has which snafu. Thus there are many targeted therapies – some approved, and hundreds more in clinical trials – but relatively few biomarkers. That lack of biomarkers leads to a problem, succinctly summarized by Cesano: "The therapy is targeted, but the patient is not."

The most naïve proposition might be that if a therapy is molecularly targeted, then by definition its molecular target could be a biomarker. But that simple relationship does not hold, according to Scott Allocco, president of BioMarker Strategies LLC. Allocco said molecularly targeted agents "have very specific targets. But actually, what they are targeting is not just that protein . . . targeted therapies are trying to disrupt signal transduction networks." A static biomarker – even one that is also the target for the therapy – is only a limited clue to how active signal transduction pathways will be. It's one reason why only half of breast cancer patients who overexpress Her2 show an objective response to Herceptin (trastuzumab, Genentech Inc./Roche AG).

Both Nodality and BioMarker Strategies believe the key to getting a handle on those signal transduction networks is changing the way in which tumor samples are treated.

Currently, tissue samples are fixed – that is, killed – as soon as they are removed from the patient, which of course makes their signal transduction pathways, and any good biomarkers in them, impossible to test afterwards. Nodality, Cesano said, is focused on analyzing biomarkers from blood samples to "reveal the relationship between biology and drug response," both in blood cancers and diseases that have an inflammation component, which includes immunological disorders.

Nodality ultimately plans to extend its work into solid tumors, possibly through the analysis of circulating tumor cells. Applying their methods to solid tumors is "reasonable, and our intention," Cesano said.

BioMarker Strategies is focused on the challenges of solid tumors, which make up 90 percent of the cancer market. Those challenges, Douglas Clark told BioWorld Insight, include the heterogeneity of the tumors, which can confound analysis, and more generally the need to "be effective utilizing relatively small amounts of cells." Clark is director of the division of cytopathology at Johns Hopkins University and chief scientific officer of BioMarker Strategies.

"We want as much information as possible," Clark said, and diagnostic biomarkers are "the bridge" to getting that information from the tumor.

Currently, however, tumor samples are often a bridge to nowhere as far as preserving biomarkers is concerned. Current methods for handling biopsies were developed in the Civil-War era and have not changed much since. They are aimed at preserving tissue for the microscope – and in those preservation methods, Clark said, "each step actually robs the tumor of information."

The company is developing a platform, SnapPath, that addresses the challenges specifically of getting and keeping live cells from solid tumor specimens, which can then be stimulated to see which signal transduction pathways are active in a patient. The company expects to have its technology available for use in clinical trials in late 2011.

Long term, Allocco said, the company believes that analyzing living tumor samples will be used not just to stratify patients for clinical trials, but to guide treatment decisions for all cancer patients. Use of the technology in clinical trials, he said, is "a stepping stone" on the way to general use.

Since the whole point of such sampling is to capture the changing nature of tumor cells, patients will need to have repeat biopsies. Clark said that most of those biopsies could be minimally invasive and "extremely tolerable" – and cancer patients, he added, tend to have the attitude that "if you can give me any information at all that helps guide my treatment, I am happy to go through this."