Research Highlights

doi:10.1038/nindia.2012.192 Published online 28 December 2012

New anti-cancer molecule

Researchers have discovered a novel anti-cancer molecule (SCR7) that can inhibit a DNA repair pathway known as non-homologous end-joining. The finding has a potential to be turned into a novel therapy for treatment of cancer.

SCR7 has been shown to impede tumor progression in mouse models and when co-administered with chemo- and radiotherapeutic agents, to enhance their sensitivity significantly.

DNA Ligase IV is responsible for sealing of double-strand breaks during the DNA repair pathway. The scientists worked on the premise that inhibiting Ligase IV could result in amassing of the breaks, thereby serving as a strategy toward treatment of cancer.

They identified SCR7 as inhibiting the joining of DSBs in a cell-free repair system. SCR7 blocks Ligase IV-mediated joining by interfering with its DNA binding but not that of T4 DNA Ligase or Ligase I, they report.

SCR7 inhibits the joining in a Ligase IV-dependent manner within cells, and activates the intrinsic apoptotic pathway. More importantly, SCR7 impedes tumor progression in mouse models and when co-administered with DSB-inducing therapeutic modalities enhances their sensitivity significantly, the researchers say.

This inhibitor to target non-homologous end-joining could offers a strategy toward the treatment of cancer and improvement of existing regimens.

The authors of this work are from: Department of Biochemistry, Indian Institute of Science, Bangalore; Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Bangalore; Institute of Bioinformatics and Applied Biotechnology, Bangalore; and Advanced Centre for Treatment, Research and Education in Cancer, Navi Mumbai, India.


References

  1. Srivastava, M. et al. An Inhibitor of Nonhomologous End-Joining Abrogates Double-Strand Break Repair and Impedes Cancer Progression. Cell. 151, 1474-1487 (2012) | Article | PubMed |