Background: Breast and ovarian cancers are among the most common and deadly gynecologic malignancies. Today, interest in the non-cytotoxic drug development is at an all-time high, albeit platinum-based combination chemotherapy is still the standard of care for ovarian cancer. However, the treatment of advanced malignancies is restricted due to chemotherapy resistance, which in most cases is acquired. Therefore, identifying novel anti-cancer strategies for gynecological cancers is imperative. We have developed a highly tumor-targeting oncolytic adenovirus by controlling its replication via tumor-specific promotor, survivin. Hitherto, we have tested the anti-tumor potency of this genetically engineered oncolytic virus against breast and lung cancers and found it very toxic and tumor-targeting. In the present study, we continued our investigation of using survivin responsive conditionally replicating adenovirus (CRAd) to chemotherapy-resistant cancers of different origins.