2023 World Conference on Lung Cancer (Posters)-EP03.06. Development of an Inhibitor for the Treatment of Lung Cancer

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Researchers at Queensland University of Technology in Australia have developed a potential inhibitor for the treatment of non-small cell lung cancer (NSCLC). The current treatments for NSCLC often lead to resistance, so new therapeutic targets are needed. The researchers focused on the DNA damage response (DDR), a network of signaling pathways involved in the detection and repair of DNA. They discovered that the DNA repair protein COMMD4 is dysregulated in NSCLC and plays a role in chromatin remodeling after DNA damage.<br /><br />Using molecular dynamics and in vitro experiments, the researchers identified the binding pose of COMMD4 and the histone protein H2B, which regulate chromatin modification. They then developed a small molecule inhibitor of the COMMD4-H2B complex. In cell viability and DNA repair assays, the inhibitor showed on-target activity, reducing cell viability and impairing DNA repair in NSCLC cells.<br /><br />The researchers also found that high expression of COMMD4 is associated with poor survival in NSCLC patients. Depletion of COMMD4 reduced proliferation and induced apoptosis in NSCLC cells but had no effect on normal bronchial epithelial cells.<br /><br />Further experiments showed that the inhibitor prevented the formation of the COMMD4-H2B complex and decreased cell viability in NSCLC cells. The inhibitor also showed potential in clonogenic cell viability experiments.<br /><br />This research highlights the potential of targeting COMMD4-H2B as a therapeutic strategy for NSCLC, with the aim of reducing toxicity and improving treatment outcomes for patients with this aggressive form of lung cancer.

Asset Subtitle

Amila Suraweera

Meta Tag

Speaker Amila Suraweera

Topic Tumor Biology: Translational Biology - Translational Therapeutics

Keywords

Queensland University of Technology

non-small cell lung cancer

NSCLC

inhibitor

DNA damage response

COMMD4

chromatin remodeling

histone protein H2B

cell viability

DNA repair