HtrA1 protein contributes to the development of resistance to chemotherapy in ovarian and gastric cancers

While many cancer patients initially have a favorable response to chemotherapy for the treatment of solid tumors, resistance to treatment often develops. Resistance can be caused by many factors, including metabolism of the drug, a decrease in drug accumulation in tumor cells, altered expression of molecules involved in cell death, or further DNA mutation or modification that makes the drug ineffective. In a study appearing online on June 8 in advance of print publication in the July issue of the Journal of Clinical Investigation, Viji Shridhar and colleagues from the Mayo Clinic College of Medicine show that 2 antitumor agents, cisplatin and paclitaxel, increase the expression of the protein HtrA1 in ovarian carcinoma cells, which induces cell death. Conversely, reduced HtrA1 expression reduced the effectiveness of cisplatin and paclitaxel.

The authors went on to test whether the level of HtrA1 expression could predict the response to chemotherapy of patients with ovarian or gastric cancer receiving cisplatin-based chemotherapy. The authors found that patients with ovarian or gastric tumors expressing higher levels of HtrA1 showed a better response to chemotherapy compared to those with lower levels of HtrA1 expression. The study reveals a novel pathway by which HtrA1 mediates the ability of chemotherapeutic agents to kill cancer cells, and suggests that loss of HtrA1 in ovarian and gastric cancer may contribute to the development of resistance to chemotherapy.

TITLE: Serine protease HtrA1 modulates chemotherapy-induced cytotoxicity

AUTHOR CONTACT:
Elizabeth Zimmermann
Communications, Mayo Clinic Cancer Center, Rochester, Minnesota, USA.
Phone: (507) 284-5005; E-mail: newsbureau@mayo.edu.

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Contact: Brooke Grindlinger
press_releases@the-jci.org
212-342-9006
Journal of Clinical Investigation
8-Jun-2006