Thymine DNA Glycosylase as a Novel Target for Lung Cancer

Abstract

The purpose of this research is to develop novel therapeutics for lung cancer (LC) based on targeting the dual DNA repair and epigenetic factor Thymine DNA Glycosylase (TDG). In principle, inhibiting TDG may both disrupt DNA repair and the cancer epigenetic state of LC cells, thus achieving a therapeutic effect that enhances the actions of existing chemotherapies and is complementary to current epigenetic therapyagents. In the current reporting period, we collected triplicate DNA and RNA samples from control and TDG knockdown A549 and H1299 lung cancer cells, in preparation for methylome and transcriptome studies. We also discovered that cells depleted of TDG have a phenotype of altered genomic stability involving mitotic function, which was completely unpredicted. Based on this discovery, in future experiments, wewill evaluate the cytotoxicity of lung cancer cells treated with first-generation TDG inhibitors, as originally proposed, but in combination with anti-mitotic drugs.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2019
Accession Number
AD1094788

Entities

People

  • Alfonso Bellacosa
  • Timothy J. Yen

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Artificial Satellites
  • Biological Aging
  • Biomedical Research
  • Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemotherapy
  • Genetics
  • Inhibitors
  • Lung Cancer
  • Medical Personnel
  • Neoplasms
  • Ovarian Cancer
  • Professional Development
  • Proteins
  • Therapy

Fields of Study

  • Biology

Readers

  • Molecular and genetic basis of cancer.
  • Oncology (Cancer Research).

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech