Junran Zhang, M.D., Ph.D.

Institution: The Ohio State University College of Medicine

Project: Inhibiting Enzyme Required for Cholesterol Synthesis May Suppress Growth of NSCLC

Grant(s): Lung Cancer Discovery Award

A large majority of lung cancers are non-small cell lung cancer (NSCLC). An enzyme required for cholesterol synthesis called squalene epoxidase (SQLE) is frequently overexpressed in NSCLC and is associated with poor patient prognosis. We will test a compound that inhibits SQLE, along with compounds that inhibit certain proteins required for DNA damage response (DDR). We will test whether inhibiting SQLE renders cells sensitive to inhibitors targeting DDR. Co-administration of a SQLE inhibitor and DDR inhibitors could work together to suppress the growth of NSCLC expressing high levels of SQLE. Our studies could lead to novel treatments for this type of lung cancer.

Update:

Our preliminary data suggest that SQLE inhibition leads to increase in squalene accumulation which is a potential reason that cause DNA damage and replication stress, rendering NSCLC cells sensitive to inhibitor targeting replication stress response protein.  Our anticipated results will provide the evidence to explain why NSCLC cells with overexpressed SQLE are sensitive to inhibitors targeting SQLE and the replication stress response proteins in combination. Identifying a novel treatment strategy will improve current lung cancer treatment plans and will help to achieve our ultimate goal of saving patient lives. 

Supported by the Mary Fuller Russell Fund

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