Researchers at the Walter and Eliza Hall Institute in Melbourne have uncovered how nutlins, a type of small molecule inhibitor, contribute to cell death in cancer cells. Until now, it was unknown whether nutlins were killing the cancerous cells or suppressed them temporarily.
In early clinical trials for treating blood cancers, Dr Liz Valente, Dr Brandon Aubrey, Professor Andreas Strasser and team discovered that nutlins are able to stop cancer growth by activating the body’s natural cancer-suppressing mechanism. They stimulate a gene called P53 to trigger programmed cell death of blood cancer cells while avoiding some of the damaging effects of chemotherapy.
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. They also provided invaluable information for a more personalised 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,” Dr Aubrey said.
“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.”
Professor Strasser said previous research around P53 showed that one of the properties of the gene was to protect the healthy cells in the body. The gene has been identified as a major barrier to developing cancer.
“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 more about what nutlins were capable of was a critical step towards developing more refined treatments for cancer.
“By understanding how nutlins are killing cancer cells, we can begin to formulate their best possible use, including choosing the best partner drugs to combine the nutlins with,” Professor Strasser said.
The Australian Cancer Research Foundation has supported WEHI by providing three grants, totalling AUD 5.5million towards cutting edge cancer research equipment and technology.
In the video below Dr Brandon Aubrey tells more about nutlins.
Image of Dr Brandon Aubrey courtesy of WEHI.