Dr Hartwich on Preclinical Findings for Y3 Plus Chemotherapy in Ovarian Cancer

Yang Yang-Hartwich, PhD, associate professor, Obstetrics, Gynecology and Reproductive Sciences, Yale Cancer Center, discusses a preclinical study delving into the mechanisms underlying chemoresistance in ovarian cancer and the potential use of a benzenesulfornamide compound named Y3 to enhance the efficacy of standard chemotherapeutic agents.

The study aimed to elucidate how Y3 sensitizes ovarian cancer cells to carboplatin and paclitaxel and if its use could induce immunogenic cell death.

Hartwich explains that patient-derived ovarian cancer cell lines were utilized to investigate the effects of Y3 pretreatment followed by carboplatin or paclitaxel administration. Findings presented at the 2024 AACR Annual Meeting showed that over the course of the study, Y3 pretreatment resulted in a decrease in the IC50 values for carboplatin and paclitaxel in ovarian cancer cell lines. Annexin VI staining revealed an increase in apoptotic cell populations in the Y3-pretreated groups compared with chemotherapy alone.

In the in vivo vaccination assay, mice administered Y3/carboplatin co-treated cells exhibited significantly suppressed tumor growth compared with the control group, Hartwich explains. Hartwich notes that these findings suggest that Y3 enhances the sensitivity of ovarian cancer cells to carboplatin and paclitaxel by activating the AMPK pathway.

Furthermore, Y3 enhances the immunogenicity of carboplatin-treated ovarian cancer cells, potentially contributing to improved therapeutic outcomes in ovarian cancer, she adds. These results provide valuable insights into the development of novel therapeutic strategies for overcoming chemoresistance in ovarian cancer, Hartwich concludes.