PARP inhibitors plus chemotherapy may be effective for Ewing sarcoma

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According to a new study published in the journal Cell Reports, researchers at St. Jude Children's Research Hospital in Memphis, Tennessee, have found that a combination of experimental drugs caused Ewing sarcoma tumors to disappear in mice, and those tumors did not return in more than 70% of those mice.

For the study, the researchers treated mice with Ewing sarcoma with poly-ADP ribose polymerase (PARP) inhibitors in addition to chemotherapy. PARP inhibitors work by interfering with DNA repair, thereby causing cancer cell death.

Mice were treated with irinotecan, temozolomide, and one of three PARP inhibitors currently in development for pediatric cancer treatment. The researchers found that Ewing sarcoma disappeared and not relapsed in over 4 months in about 70% of mice treated with irinotecan, temozolomide, and olaparib. Olaparib is an investigational PARP inhibitor currently being studied for the treatment of breast and ovarian cancers. Mice treated with the same chemotherapy plus talazoparib, another PARP inhibitor, achieved a complete remission rate of 88%.

The researchers plan to conduct clinical trials testing irinotecan and talazoparib in patients age 1 and older and the three-drug combination therapy in patients age 16 and older with Ewing sarcoma.

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A combination of experimental drugs caused Ewing sarcoma tumors to disappear in mice.

Ewing sarcoma tumors disappeared and did not return in more than 70 percent of mice treated with combination therapy that included drugs from a family of experimental agents developed to fight breast cancer, reported St. Jude Children's Research Hospital scientists. The study will appear in the November 6 edition of the scientific journal Cell Reports.

The treatment paired two chemotherapy drugs currently used to treat Ewing sarcoma (EWS) with experimental drugs called poly-ADP ribose polymerase (PARP) inhibitors that interfere with DNA repair. PARP inhibitors are currently in clinical trials for the treatment of certain breast and ovarian cancers as well as other solid tumors. EWS is a cancer of the bone and soft tissue that strikes primarily adolescents and young adults.

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