Cancer breakthrough

MELBOURNE researchers have uncovered how a key cancer-fighting gene — one that is involved in at least half of all cancers globally — works to stop cancer growth.

The findings of the international study, led by the Walter and Eliza Hall Institute of Medical Research, could lead to more effective treatments, allow doctors to better know what cancers will become more aggressive following chemotherapy, and help diagnose patients earlier.

This key gene, called p53, is present in every cell in the body and has the job as the “master regulator” of cell growth and death. Cells across the body are constantly dividing and multiplying, in which mistakes can be made when passing on DNA from one generation of cells to the next.

DNA repair mechanisms fix these mistakes so there aren’t genetic mutations, to best prevent consequences such as cancer. When p53 becomes mutated or faulty, it can no longer suppress the growth of tumours.

Co-lead author Dr Ana Janic said using mice models of the blood cancer lymphoma, her team used sophisticated genetic screening to look at processes down the chain of p53 and uncovered, for the first time, a number of other genes involved in DNA repair that are crucial to its function.

When these other genes were removed, p53 couldn’t function properly and lymphoma developed. When the gene was returned, tumour development was significantly thwarted.

“This gene was discovered about 25 years ago, but until now we haven’t known that DNA repair is the major process that is critical for p53 to work as a tumour suppressor,” Dr Janic said.

“This has real outcomes for patients. The p53 mutated tumour doesn’t usually respond to chemotherapy, it actually becomes more aggressive.

Dr Janic, who led the work alongside Associate Professor Marco Herold and Professor Andreas Strasser, said understanding how p53 worked was the “holy grail” in cancer research. It is mutated in about 70 per cent of colon and pancreatic cancers, and in almost every type of ovarian cancer.