"Northwestern Medicine scientists have discovered how a specific transcription factor promotes genetic reprogramming and chemotherapy resistance in ovarian cancer cells, findings that may inform new targeted treatment approaches that inhibit this process and improve patient outcomes, according to a recent study published in The Journal of Clinical Investigation. Mazhar Adli, PhD, the Thomas J. Watkins Memorial Professor of Tumor Genomics, was senior author of the study."
"Chemotherapy resistance remains an urgent challenge in treating high-grade serous ovarian cancer, the most common type of ovarian cancer. Therefore, identifying the molecular mechanisms utilized by ovarian cancer cells in the early stages of chemoresistance could help significantly improve patient outcomes, according to Adli. Previous work led by Adli established that the SOX9 protein is a super-enhancer regulated transcription factor whose expression is significantly upregulated in chemoresistant ovarian cancer cells."
SOX9 is epigenetically upregulated in response to chemotherapy treatment in ovarian cancer cell lines. SOX9 functions as a super-enhancer regulated transcription factor whose expression is significantly increased in chemoresistant ovarian cancer cells. Multiomics, tumor microarrays, and epigenetic modulation were used to define the role of SOX9 in driving and maintaining chemoresistance. Chemotherapy resistance remains an urgent therapeutic challenge in high-grade serous ovarian cancer and contributes to high mortality. Identifying molecular mechanisms of early-stage chemoresistance enables development of targeted interventions. Inhibiting SOX9-driven reprogramming represents a promising strategy to overcome resistance and improve patient outcomes.
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