Victorian researchers have unlocked an important puzzle surrounding the operation of a new class of anti-cancer drugs work, opening up new ways of treating cancer.
Called, nutlins, the new drugs are in early clinical trials for treating blood cancers.
This has sparked worldwide excitement because of their ability to stop cancer growth by activating the body's natural cancer-suppressing mechanism – a gene called P53.
Importantly, nutlins also avoid some of the damaging effects of chemotherapy.
Until now, no one knew if nutlins killed cancerous cells or just suppressed them.
The discovery was made by Dr Liz Valente, Dr Brandon Aubrey, Professor Andreas Strasser and colleagues from the Walter and Eliza Hall Institute. They found that nutlins cause cancer cells to self-destruct rather than be put to sleep.
The research, published in the journal Cell Reports, revealed that nutlins activated P53 to trigger programmed cell death (apoptosis) of blood cancer cells. This was identified through the presence of a protein called PUMA.
Dr Aubrey, who is also a clinical haematologist at The Royal Melbourne Hospital, said the discovery reinforced that nutlins were a promising new treatment for blood cancer. It also provided invaluable information for a more tailored approach to patient care.
"Our findings will help identify which patients are most likely to benefit from nutlins and which types of cancers are most likely to respond to nutlins as a treatment. Understanding in detail how the drugs work will help in the design of better clinical trials and bring the world closer to more precise and personalised medical treatments for cancer," Dr Aubrey said.
Professor Strasser said previous research around P53 showed the gene was like a natural 'guardian' of healthy cells in the body and was a major barrier to developing cancer.
"P53 acts by either halting the cell while repairs are made or by forcing the cell to die if it cannot be repaired. Without the 'help' of P53, a damaged cell can be allowed to multiply, leading to cancer development.
"P53 lies dormant in many types of cancer – that do not have mutations in P53 – and the nutlins work through re-awakening its activity."
Professor Strasser said knowing what nutlins were capable of by identifying how nutlins were activating P53 to trigger cell death in cancers was a critical step towards developing more sophisticated treatments for cancer.
Dr Aubrey is a PhD student at the Walter and Eliza Hall Institute enrolled through The University of Melbourne's Department of Medical Biology. Professor Strasser is a joint division head in the Molecular Genetics of Cancer division at the Walter and Eliza Hall Institute.