Exploiting Tumor-Activated Testes Proteins to Enhance Efficacy of First-Line Chemotherapeutics in NSCLC
Technical Report,30 Sep 2014,29 Sep 2015
University of Texas Southwestern Medical Center Dallas United States
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Cancer Testis Antigens CTAs are a group of proteins whose expression is restricted to reproductive tissues testis and ovaries, but frequently activated in Non Small Cell Lung Cancer NSCLC. A number of these CTAs are essential for meiosis during spermatogenesis. Their deletion in mice leads to infertility due to an inability to repair DNA Double Strand breaks DSB during homologous recombination in meiosis. DSBs frequently occur in the tumorigenic environment due to environmental insults such as hypoxia and reactive oxygen species. We hypothesize that CTAs promote repair of these DSB in NSCLC and are essential for tumor cell survival. To evaluate this hypothesis, we are investigating the biochemical, cell biological and in vivo activity of CTAs in NSCLC. We have identified CTAs that are essential for DNA DB in NSCLC and which are also essential to survival of these cells in vitro. We find that the expression of meiotic CTAs appears to be a marker for the inactivation of metabolic pathways that lead to the generation of DNA-damage species. These findings are under testing in vivo. The physical interaction network of CTAs and identification of additional CTAs that may mediate sensitivity to DNA damage inducing drugs is under investigation.