Is a Putative Therapeutic Target for -Mutated Ovarian Clear Cell Carcinoma.

BACKGROUND

Ovarian clear cell carcinoma (OCCC) is resistant to platinum chemotherapy and is characterized by poor prognosis. Today, the use of poly (ADP-ribose) polymerase (PARP) inhibitor, which is based on synthetic lethality strategy and characterized by cancer selectivity, is widely used for new types of molecular-targeted treatment of relapsed platinum-sensitive ovarian cancer. However, it is less effective against OCCC.

METHODS

We conducted siRNA screening to identify synthetic lethal candidates for the mutation; as a result, we identified Cyclin-E1 () as a potential target that affects cell viability. To further clarify the effects of , human OCCC cell lines, namely TOV-21G and KOC7c ( mutant lines), and RMG-I and ES2 ( wild type lines) were transfected with siRNA targeting or a control vector.

RESULTS

Loss of reduced proliferation of the TOV-21G and KOC7c cells but not of the RMG-I and ES2 cells. Furthermore, in vivo interference of effectively inhibited tumor cell proliferation in a xenograft mouse model.

CONCLUSION

This study showed for the first time that is a synthetic lethal target gene to -mutated OCCC. Targeting this gene may represent a putative, novel, anticancer strategy in OCCC treatment.