ANU Professor Mark Polizzotto heads up a world-first cancer trial. Photo: Jack Fox/ANU.
Some researchers refer to MYC-driven cancers as notorious and infamous. They’re difficult to treat and aggressive, and attempts to treat them by inhibiting the MYC gene have stalled in the past.
But now a world-first trial in Canberra will target the infamous “undruggable” cancer gene with a newly developed MYC inhibitor drug – PMR-116.
Leading the trial, Australian National University (ANU) Professor Mark Polizzotto said most cancers including prostate, breast, ovarian and haematological were connected to this gene.
“Approximately 70 per cent of all cancers are fuelled by abnormal MYC activity,” Professor Polizzotto said.
“MYC is one of the most notorious cancer-causing genes, and tumours driven by MYC overexpression are often among the most aggressive and difficult to treat.”
It’s hoped PMR-116 represents a breakthrough in treating these aggressive cancers. ANU will trial the drug in collaboration with Canberra Hospital, Peter MacCallum Cancer Centre in Victoria, and St Vincent’s Hospital in Sydney. If successful, the drug could make a big difference in the treatment of cancer.
What makes this trial a world first is that it marks the first time an MYC inhibitor drug will be tested in a basket trial – meaning it will be tested on a number of cancer types at the same time. The trial also uses a unique method to target the gene through RNA (ribonucleic acid) production.
ANU Professor in Cancer Biology, Professor Ross Hannan, who helped develop the drug, said targeting the gene for cancer treatment was thought to be almost impossible.
“MYC has long been considered ‘undruggable’, but early results of PMR-116 show promise in changing that perception,” he said. “PMR-116 targets MYC-driven cancers by inhibiting an enzyme to disrupt ribosomal biogenesis – a crucial process hijacked in these cancers.”
MYC’s disordered structure has made it difficult to target and experts admit they still have a “surprisingly limited” understanding of it despite a large body of literature. But this is fast changing, according to a paper published in the scientific journal Nature.
“In recent years, attempts to develop MYC inhibitors have multiplied and the first clinical trials have been testing their efficacy in patients. We are finally reaching the point at which its inhibition seems clinically viable,” stated MYC in cancer: from undruggable target to clinical trials.
According to a 2014 paper, many cancers appear to become “addicted” to MYC, which contributes to their fast growth and persistence. MYC inhibitors, therefore, could be a game changer for cancer treatment.
The ANU study isn’t the only clinical trial in the world for MYC inhibitors, but it’s hoped PRM-116 could be one of the first to be a viable cancer treatment.
The Canberra trial will get underway later this year. Research has been funded by the Medical Research Future Fund, part of Australia’s sovereign wealth fund and developed by the ANU in collaboration with pharmaceutical company Pimera Therapeutics.
