Targets for cancer treatment

Most cancer cells trigger cell death in response to chemotherapy but some opt to stall their growth to keep themselves alive. The study, headed up by Professor Carlos Caldas, from the Cancer Research UK Department of Oncology at the University of Cambridge, found that a protein molecule called p300 was key to determining whether cancer cells would live or die when exposed to anti-cancer treatments.

Experts believe blocking the action of the molecule could help increase the sensitivity of cancers to chemotherapy and may lead to ways to predict which patients will respond to treatment.

Scientists knew p300 was involved in regulating a gene called p53 - known as the guardian of the genome. The gene protects normal cells from the effects of DNA damage that could lead to cancer. If cells look like they may turn cancerous p53 suspends their growth or triggers their suicide mechanism.

Anti-cancer drugs, which work by damaging DNA, exploit this mechanism in cancer cells with an intact p53 gene. When tumours are exposed to chemotherapy p53 is activated so that the cancer cell dies or stops growing. But what determines whether the cancer cell is successfully killed off or just put to sleep has remained unclear until now.

In the new study researchers compared the effect of UV radiation on human cancer cells that had p300 and those that were missing the molecule. They found that cells with p300 only partially activated p53 and stopped growing but remained alive. However, cells without p300 could fully activate p53 and trigger their suicide mechanism in response to DNA damage.

The team also tested the effect of a number of chemotherapy agents on cells with and without p300 and found the same effect: cells with p300 frequently failed to die whereas identical cells lacking p300 triggered their suicide machinery.

Professor Caldas said: