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Indication Expansion and Repurposing of PIK3CA Kinase Inhibitors: Systems Analysis of Alpelisib and Oral Cancers
Here we demo tools to rapidly guide drug repurposing and indication expansion, using alpelisib—a PI3Kα inhibitor approved for metastatic breast cancer—as a case study. The speaker shows how activating mutations in the PIK3CA gene, a key oncogene, not only prevalent in breast cancer but also significantly present in oral cancers, an area with few active clinical trials and limited therapeutic development. By merging real-world mutation data, clinical outcomes, and pathway-based network modeling, the analysis shows that PIK3CA mutations in oral cancer correlate with poorer survival, and that inhibiting PIK3CA activity could reduce disease progression. Further, the session used public dataset comparisons to identify non-oncologic diseases (e.g., lupus, heart disease) that share similar biology, suggesting future repurposing potential. It concluded by identifying possible combination therapy partners through anti-matching expression patterns, showcasing a full workflow from hypothesis generation to target validation in under an hour.
24:12 minutes
Tags: biomarker, cancer_drug_discovery, hsmd, oncology