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PGRN Study Finds Biomarkers of Camptosar Response Not Consistent by Tissue of Origin

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Protein biomarkers of tumor response to Pfizer's chemotherapeutic Camptosar vary according to each tumor's individual properties, rather than to tissue of origin, according to research conducted by members of the Pharmacogenetics Research Network at the Washington University School of Medicine in St. Louis. The implication is that cancer treatment regimens may be more effective when informed by diagnostic data, as opposed to the traditional method of basing therapy on anatomical location.

"This is the first time markers [have been compared] across different tissue types to see whether the drug markers are independent of anatomy," Howard McLeod, director of the pharmacology core at the Siteman Cancer Center, and a member of the PGRN, told Pharmacogenomics Reporter this week.

The PGRN group measured the levels of 11 different protein markers of Camptosar (irinotecan) toxicity, activity, and efficacy in 255 cancer samples from eight different tissues of origin. Using these markers, the group attempted to predict the anatomical location from which each tumor arose. "You basically can't do it — the markers are not tracking with the anatomy," said McLeod.

Tumors from colon, breast, prostate, ovary, lung, brain, melanoma, and lymphoma each showed large variability in biomarker levels within their tissue-of-origin type.

The group's research will be printed in the upcoming issue of the Journal of Pathology.

Should research continue to point to biomarkers as better guides for prescribing drugs, traditional methods of treating cancer may have to change from an approach based on tissue of origin to one based on tumor biomarkers, although the level of evidence needed would have to be "very high," said McLeod.

Tissue-of-origin-based therapies "are not that effective if you just give them to everybody," whereas marker-driven therapy should be able to "really enrich the chance of having some benefit," he added. Currently, "we barely get it right half the time."

McLeod stressed, however, that in the PGRN study, the researchers were not looking at response to chemotherapy, but were "looking at protein markers that are associated with the efficacy of the drug."

The next step in research will be to perform similar studies for markers related to different drugs, as well as to replicate the current study on a smaller number of tumor types. "With this sort of data, we then can move toward the day when we can do a trial, randomizing patients to marker-driven therapy versus anatomy-based therapy," said McLeod. He said he could not estimate when the PGRN might be able to begin such a trial.

McLeod's group is also planning to collaborate with "companies that perform chemotherapy sensitivity testing" to try to determine which drugs would be best for patients without ideal markers of irinotecan response.

— Chris Womack ([email protected])

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