Biological Markers Found That Correlate To Esophageal Cancer Treatment Success

to therapy, Harpole found the three protein markers whose presence or absence significantly impacted patient survival.

The presence of one such marker, P-glycoprotein (Pgp), signaled that the patients would not respond well to chemotherapy. Pgp is primarily responsible for inducing multi-drug resistance, in which the tumors become resistant to many chemotherapy drugs after treatment with just one drug. Pgp effectively pumps the drug out of tumor cells before it has time to kill the cells. Pgp is just one protein implicated in multi-drug resistance. Harpole found that the 88 patients with Pgp survived 20.9 months on average, while the 24 patients without Pgp had an average survival of more than 5 years after diagnosis.

Laboratories across the country are looking into ways to stop Pgp or to circumvent its action. One way is to give patients Pgp modulators -- molecules that block Pgp=s drug pump. Another is to develop drugs that Pgp and related proteins can=t remove from the cell.

A second significant marker was glutathione-s-transferase-pi, or GST-pi, which confers radiation resistance. Radiation kills cells by forming oxygen radicals -- highly reactive oxygen atoms that damage DNA. GST-pi reduces these oxygen atoms so that they are no longer reactive. The 84 patients with GST-pi survived an average of 21 months, while those without it survived 47 months on average.

The third implicated marker was HER-2/neu, which initiates chemical signals telling the cell to multiply. Herceptin, a drug recently approved by the FDA to treat breast cancer patients who have excess HER-2/neu, or other agents might eventually be useful in esophageal cancer, Harpole said. Average survival for the 94 HER-2/neu positive patients was 26.8 months, while that for HER-2/neu negative patients was 14.5 months.

The researchers are continuing to study molecular markers, both in esophageal cancer and in lung cancer -- two diseases with survival rates relatively constan

Contact: Joanna Downer
Duke University Medical Center

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