The seeming invincibility of cancerous tumors may be crumbling, thanks to a promising new gene therapy that eliminates the ability of certain cells to repair themselves. Researchers at the Cornell University College of Veterinary Medicine have discovered that inactivation of a DNA repair gene called Hus1 efficiently kills cells lacking p53 — a gene mutated in the majority of human cancers.
Using a mouse model, senior author Robert Weiss, associate professor of molecular genetics, first author and graduate student Stephanie Yazinski and colleagues explored how cells respond when both genes are inhibited. When they inactivated the Hus1 gene in healthy mammary gland tissues, the researchers report, it caused genome damage and cell death. And when they studied the effects of Hus1 inactivation in p53-deficient cells, which are highly resistant to cell death, they discovered that the ability of Hus1 inactivation to kill cells was even greater.
The study is published in the Proceedings of the National Academy of Sciences (Nov. 9).
“Our work contributes to an important new understanding of cancer cells and their weaknesses,” Weiss said. “The mutations that allow cancer cells to divide uncontrollably also make the cancer cells more dependent on certain cellular processes. We were able to exploit one such dependency of p53-deficient cells and could efficiently kill these cells by inhibiting Hus1.”
Weiss and his team have new experiments under way. “We’ve proven the power of inhibiting both pathways in normal tissue,” said Weiss. “Now we want to extend our knowledge to cancerous tissue and determine if the loss of Hus1 will impact the ability of cancers with p53 mutations to take hold and grow.”