Zih-Yin Lai
National Tsing Hua University, Taiwan
Title: Combination strategy of drug repositioning for neuroendocrine cervical carcinoma treatment
Biography
Biography: Zih-Yin Lai
Abstract
Precision cancer medicine is an evolving treatment approach that aims to associate the tumor’s unique genomic characters and histological changes to first determine the cancer subtype, and use the information to select targeted therapy for enhanced efficacy. In this study, we focus on neuroendocrine cervical carcinoma (NECC), which is a rare and aggressive subtype of cervical cancer. A NECC specimen obtained from a consented 44-year-old female patient was first analyzed by RNA sequencing. Interestingly, we found the transcription profile of the tumor case highly correlated with metabolic disease. Meanwhile, we processed and established a novel NECC cell line (annotated as Hsinchu Mackay-4, HM-4) from the patient’s ex vivo biopsy, and used it to explore novel drug combination for enhanced cytotoxic response. Drug screening revealed that, when etoposide (a known genotoxic drug for NECC) was used in combination with agent X (an FDA-approved metabolic disease drug), the proliferation of HM-4 cells was significantly inhibited as compared to etoposide or agent X treatment alone. Immunoblot assay revealed the expression level of pAKT was remarkably reduced, while p21 was upregulated when HM-4 cells were treated with a combination of etoposide and agent X. These results suggested that the drug combination of etoposide and agent X might become a novel synergistic treatment option for NECC.