Repress cancer growth and sensitize cancer cells to DNA damage therapy




Mode Of Action

Inhibition of Cut-Like Homeobox 1(CUX1)

Main Advantages

  • Potential therapeutic benefit to patient with RAS-driven cancers
  • CUX1 is not essential to normal cells, but is absolutely required for survival in situations of severe genotoxic stress such as that caused by reactive oxygen species in RAS-driven cancer cells or by DNA-damaging cancer treatments
  • Could avoid severe adverse effects on normal cells typically observed by direct inhibition of base excision repair enzymes
  • Small molecules that inhibit the ability of CUX1 to stimulate base excision repair enzymes are expected to treat RAS-driven cancers with an improved therapeutic window


Goodman Cancer Research Centre at McGill University


Disease Facts / Medical Need

  • Currently there is no treatment that targets RAS-driven tumours.
  • A drug capable of interfering with the ability of CUX1 to participate in DNA repair would target many types of cancers in which reactive oxygen species are produced as a consequence of mutation in a RAS gene or any oncogene that activates the RAS pathway; such activation is seen in 59% of pancreatic cancers and some 30% of human cancers overall.

How This Target Works

Activation of the RAS pathway in cancer cells leads to higher production of reactive oxygen species, which cause DNA damage by oxidation. In turn, sustained DNA damage triggers cellular senescence. Cancer cells can adapt to such oxidative DNA damage by increasing their expression of CUX1, which stimulates the activities of two enzymes that repair oxidized bases in DNA. Knocking down the CUX1 protein has been found to kill all cancer cells that have high levels of reactive oxygen species (ROS).

For more information

Kem Payza

Project Director

© 2019 NEOMED Institute. All Rights Reserved. // Solutions Web Globalia