Targeting a gene that protects cancer cells from the lethal effects of radiotherapy could help improve the impact of treatment

Jun 21 2004

Targeting a gene that protects cancer cells from the lethal effects of radiotherapy could help improve the impact of treatment, a leading Cancer Research UK scientist will tell conference delegates in Glasgow this week.

Speaking at the Cancer Research UK Beatson International Cancer Conference, Professor David Gillespie, will present his work on a gene called Chk1.

The gene helps cells repair faulty DNA. Prof Gillespie's team believes drugs that block its function could make radiotherapy, which works by damaging DNA, more effective.

Normal cells have evolved surveillance mechanisms to detect and repair DNA damage. These systems ensure faulty DNA isn't passed on when a cell divides.

But the repair kit also comes to the rescue of cancer cells when they come under attack. Prof Gillespie is one of many scientists searching for ways to prevent the repair process from working in tumours.

Prof Gillespie says: "Cells in our body are constantly suffering genetic damage and without systems to mend our DNA they would quickly die as a result. Unfortunately, the repair systems also operate in cancer cells."

Scientists know Chk1 responds to DNA damage in normal cells by stopping cell division to allow time for repair. If a cell is a football pitch and its DNA the players, the gene acts like a referee – stopping the match when a player is injured to allow time for him to be checked over.

But the Chk1 referee also acts in cancer cells, blowing the whistle in response to DNA damage caused by cancer treatments.

Prof Gillespie's team, based at The Beatson Institute for Cancer Research in Glasgow, knocked out Chk1 in cancer cells. They found that cells missing the gene were not only more sensitive to radiotherapy but also had slower growth and a shorter lifespsan.

He says: "We knew that Chk1 was involved in the DNA repair process so we looked at how cancer cells faired without the gene.

"Our results suggest that if the gene could be selectively blocked in tumour cells, treatment could be much more effective."

Professor Robert Souhami, Director of Clinical and External Affairs at Cancer Research UK, says: "Understanding how cells respond to DNA damage will identify new strategies to make tumours more susceptible to treatment.

"In the future we hope to see a new class of cancer drug emerging from targeting these DNA repair pathways."