Cell and Developmental Biology (CDB) Department

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Cell and Developmental Biology Seminar: Dr. Andrea Kasinski, Purdue Center for Cancer Research, Department of Biological Sciences, Purdue

Event Type
Cell and Developmental Biology
wifi event
Mar 9, 2022   12:00 pm  
Dr. Andrea Kasinski - Host: Dr. Stephanie Ceman
Laura Martin
Originating Calendar
Cell and Developmental Biology (CDB) Departmental Seminars

Targeted agents have shown great anti-cancer activity in the clinic, reducing unwanted toxicity. Unfortunately, the added benefit of using a targeted agent is met with acquired resistance due the specificity of the agent for a single target. Understanding mechanisms involved in resistance and developing novel agents that can overcome or avoid resistance are clearly in need. Today I will discuss our efforts in this space focusing on a histone methyltransferase, KMT5C that drives resistance to many commonly used tyrosine kinase inhibitors, including those targeting the epidermal growth factor and HER2. Our work shows that loss of KMT5C leads to activation of multiple genes that drive various bypass tracks involved in resistance, some by way of long non-coding RNAs. I will then discuss our effort to develop a holistic small RNA delivery vehicle that, when complexed with a relevant tumor-suppressor microRNA, can target multiple cancer-driving genes at once, reducing the potential for acquired resistance. Indeed some microRNAs are predicted to have potent anti-cancer activity; however, a clinically relevant delivery vehicle has been the major bottleneck at allowing us to reveal the decade-long promise of using these RNAs in the clinic. Here I will present our work using a targeted ligand-mediated approach, that includes an intramolecular endosomal escape agent, and a fully modified microRNA that collectively has superior anti-tumor activity relative to MRX34, the lipid encapsulated version of miR-34a that entered into clinical trial. 

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