Researchers Find Biomarker May Indicate Probable Response to Therapy for Ovarian and Gastric Cancers

Thursday, June 15, 2006

ROCHESTER, Minn. — Mayo Clinic researchers, in collaboration with several international teams, report that individuals respond better to cisplatin and paclitaxel chemotherapy treatments for ovarian or gastric cancer, specifically stomach cancer, when they have higher levels of the HtrA1 protein — indicating a potential clinical use of this biomarker to predict treatment response. Results of the study, which provides the first evidence of a connection between HrtA1 and chemotherapy-induced cell death, are available online in The Journal of Clinical Investigation.

"We see time and again that some individuals respond to treatment in markedly different ways from others, and we need to find out why," says Jeremy Chien, Ph.D., a Mayo Clinic laboratory medicine and pathology researcher and lead author of the study. "In this study we've been able to identify a protein whose expression was associated with the effectiveness of cisplatin and paclitaxel for ovarian and gastric cancer treatment."

Ovarian cancer, the deadliest gynecological cancer, claims over 15,000 lives each year, and stomach cancer, which affects men and women, accounts for another 11,400 deaths. Common chemotherapy treatments for these cancers are cisplatin and paclitaxel, and this study focused on their interaction with HtrA1.

Dr. Chien and other Mayo Clinic researchers previously discovered that over-expression of the HrtA1 protein causes cancer cell death (opens in new window). In the current study, the researchers show that the amount of HrtA1 in the tumor tissue influences a patient's response to the studied drugs, and that they in turn regulate the amount of HrtA1 that is expressed.

The investigators conducted laboratory and clinical testing to determine how HrtA1 affects the function of these drugs. Their goal was to identify whether the presence of HtrA1 in patient tumors could predict which patients will respond better to the chemotherapy. In the lab, they found a positive relationship between both cisplatin and paclitaxel and the expression level of this protein. HtrA1 expression was increased by chemotherapeutic drug treatment, which caused the protein to then assist in chemotherapy-induced cell death.

The team examined the expression of this protein in 60 ovarian and 51 gastric cancer patients. The ovarian cancer tumors with high levels of HtrA1 showed a 90 percent response rate (27/30) compared with 62 percent (8/13) and 65 percent (11/17) response rates in tumors with low and moderate levels of HtrA1, respectively. In gastric cancer tumors, HtrA1 levels also were important in response to treatment, with 71 percent (20/28) of patients with moderate levels of HtrA1 responding to chemotherapy compared to only 35 percent (8/23) of patients with undetectable HtrA1 levels responding to chemotherapy.

The investigative team is optimistic about these findings. "We are quite excited by the idea of a predictive biomarker," says Viji Shridhar, Ph.D., head of the research program that conducted this study. "We expect that this finding will help oncologists to tailor more effective individualized treatments, and hopefully reduce the number of deaths due to ovarian and gastric cancers." She cautions that further research should be done to confirm these findings, and hopes to see application in other tumor types as well.

Other members of the Mayo Clinic research team included Giovanni Aletti, M.D.; Gary Keeney, M.D.; Kimberly Kalli, Ph.D.; Julie Staub; William Cliby, M.D.; Yean Kit Lee; Keith Bible, M.D., Ph.D.; Lynn Hartmann, M.D.; and Scott Kaufmann, M.D., Ph.D. Collaborators included Alfonso Baldi, Ph.D., Second University of Naples, Italy; Vincenzo Catalano, M.D., and Pietro Muretto, M.D., San Salvatore Hospital, Pesaro, Italy; and Michael Ehrmann, Ph.D., Cardiff University, United Kingdom.

For more information about cancer research at Mayo Clinic, visit their homepage (opens in new window).

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