Feng Yan

Evaluating the Efficacy of Mebendazole Repurposing for Ovarian Cancer Therapy Using Optical Coherence Tomography

ABSTRACT Ovarian cancer (OvCa) remains the leading cause of gynecological cancer mortality, with most patients developing chemoresistance. Drug repurposing offers promising alternatives, with mebendazole (MBZ) showing anticancer activity. This study evaluates MBZ efficacy using Spectral Domain Optical Coherence Tomography (SD‐OCT). We conducted longitudinal imaging of 40 wild‐type (WT) and cisplatin‐resistant (CPR) OVCAR8 multicellular tumor spheroids over 11 days. Four analyses were performed: volume analysis, optical attenuation analysis, uniformity analysis, and texture feature analysis. Volume analysis showed MBZ reduced spheroid growth in both groups, with greater effects in CPR‐MCTs. Optical attenuation analysis revealed increased necrotic tissue ratios in treated spheroids. Uniformity analysis demonstrated MBZ targets heterogeneous tissues effectively. Texture analysis identified significant structural changes, with 866 altered features in CPR spheroids versus 124 in WT spheroids. Cell viability assays confirmed MBZ's effectiveness against standard and chemo‐resistant OVCAR8 tumors. This study demonstrates SD‐OCT's utility for noninvasive therapy monitoring in 3D cancer models.

Optical Coherence Tomography of Tumor Spheroids Identifies Candidates for Drug Repurposing in Ovarian Cancer

Multicellular tumor spheroids (MCTs) are indispensable models for evaluating drug efficacy for precision cancer therapeutic strategies as well as for repurposing FDA-approved drugs for ovarian cancer. However, current imaging techniques cannot provide effective monitoring of pathological responses due to shallow penetration and experimentally operative destruction. We plan to utilize a noninvasive optical imaging tool to achieve in vivo longitudinal monitoring of the growth of MCTs and therapeutic responses to repurpose three FDA-approved drugs for ovarian cancer therapy. A swept-source optical coherence tomography (SS-OCT) system was used to monitor the volume growth of MCTs over 11 days. Three inhibitors of 2-Methoxyestradiol (2-ME), AZD1208, and R-Ketorolac (R-keto) with concentrations of 1, 10, and 25 µM were employed to treat ovarian MCTs on day 5. Three-dimensional (3D), intrinsic optical attenuation contrast, and degree of uniformity were applied to analyze the therapeutic effect of these inhibitors on ovarian MCTs. We found that 2-ME, AZD1208, and R-keto with concentration of 10 and 25 µM significantly inhibited the volume growth of ovarian MCTs. There was no effect to necrotic tissues from all concentrations of 2-ME, AZD1208, and R-keto inhibitors from our OCT results. 2-ME and AZD1208 inhibited the growth of high uniformity tissues within MCTs and higher concentrations provided more significant inhibitory effects. Our results indicated that OCT was capable and reliable to monitor the therapeutic effect of inhibitors to ovarian MCTs and it can be used for the rapid characterization of novel therapeutics for ovarian cancers in the future.