Olaparib and Temozolomide

Elodie_Espesset · July 2, 2016, 6:58pm

A new study suggests that combining olaparib and temozolomide could have therapeutic benefits for the treatment of synovial sarcoma:

ncbi.nlm.nih.gov

Synovial sarcoma cell lines showed reduced DNA repair activity and sensitivity to a PARP inhibitor.

H Yamasaki, M Miyamoto, Y Yamamoto, T Kondo, T Watanabe and T Ohta, Genes to cells : devoted to molecular & cellular mechanisms, Aug 2016

Synovial sarcoma is a soft-tissue sarcoma and a rare type of cancer. Unfortunately, effective chemotherapies for synovial sarcomas have not been established. In this report, we show that synovial sarcoma cell lines have reduced repair activity for DNA damage induced by ionizing radiation (IR) and a topoisomerase II inhibitor (etoposide). We also observed reduced recruitment of RAD51 homologue (S. cerevisiae; RAD51) at sites of double-strand breaks (DSBs) in synovial sarcoma cell lines that had been exposed to IR. These findings showed that synovial sarcoma cell lines are defective in homologous recombination (HR) repair. Furthermore, we found that a poly-(ADP-ribose) polymerase (PARP) inhibitor (AZD2281; olaparib) effectively reduced the growth of synovial sarcoma cell lines in the presence of an alkylating agent (temozolomide). Our findings offer evidence that treatment combining a PARP inhibitor and an alkylating agent could have therapeutic benefits in the treatment of synovial sarcoma.

There is a phase 1 trial for Ewing sarcoma with this combination which could be interesting to follow:

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Olaparib and Temozolomide

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