Groundbreaking Clinical Trial Targets 'Undruggable' MYC-Driven Cancers

A pioneering clinical trial aimed at treating cancers deemed 'undruggable' is set to commence later this year, spearheaded by a research team from The Australian National University (ANU) in collaboration with Canberra Health Services. This innovative trial, funded by the Medical Research Future Fund (MRFF), focuses on MYC-driven cancers, a category that encompasses various malignancies including prostate, breast, ovarian, and hematological cancers.

The MYC protein, a critical regulator of cell growth, is frequently implicated in tumor development, with abnormal MYC activity fueling approximately 70 percent of all cancers, according to Professor Mark Polizzotto, a haematologist at ANU and the trial's lead investigator. He stated, "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."

The trial employs a unique design known as a 'basket trial,' which allows for the grouping of patients based on the MYC protein's involvement rather than the specific type of cancer they have. This approach is efficient, conserving both time and resources compared to conducting separate trials for individual cancer types.

The experimental drug, PMR-116, developed by Professor Ross Hannan and his team at ANU in conjunction with Pimera Therapeutics, targets a pathway downstream of the MYC protein. Early preclinical studies have shown promising results in various cancers. Professor Hannan, who holds the position of ANU Centenary Chaired Professor in Cancer Biology, explained, "PMR-116 targets MYC-driven cancers by inhibiting an enzyme to disrupt ribosomal biogenesis—a crucial process hijacked in these cancers."

Dr. Nadine Hein, who led the preclinical efforts on PMR-116, articulated the significance of this research, stating, "MYC has been the focus of cancer research for a long time, and it’s challenging to target MYC directly as it has a disordered structure. However, by blocking this critical pathway downstream of MYC, we’re now seeing remarkable results in cancers where MYC is involved."

The MRFF grant supports this ambitious initiative, which encompasses collaboration with various hospitals across Australia, including the Canberra Hospital, Peter MacCallum Cancer Centre in Victoria, and St Vincent’s Hospital in Sydney. Professor Polizzotto reiterated the trial's goal: "Our aim is to target a key driver of cancer and expedite the development of effective treatments for patients who have exhausted standard therapies."

As the trial progresses, it represents a significant leap forward in cancer research, potentially altering the treatment landscape for patients with MYC-driven cancers, who have traditionally faced limited options. If successful, PMR-116 could redefine the prospects for many individuals suffering from these challenging malignancies, marking a critical development in the ongoing battle against cancer.