Australian Researchers Launch World-First Clinical Trial of PMR-116 to Target 'Undruggable' MYC-Driven Cancers
核心洞察
A world-first clinical trial targeting MYC-driven cancers (搜索) will begin later this year, led by researchers from The Australian National University and funded by the Medical Research Future Fund.
The experimental drug PMR-116 targets approximately 70% of all cancers by inhibiting a pathway downstream of the MYC protein (搜索), which has long been considered 'undruggable' due to its disordered structure.
The basket trial design will include patients with multiple cancer types including prostate, breast, ovarian, and haematological cancers (搜索), all unified by MYC protein (搜索) involvement rather than cancer type.
A groundbreaking clinical trial targeting cancers that have long been considered "undruggable" will commence later this year, marking a significant milestone in cancer therapeutics. The world-first study, led by researchers from The Australian National University (ANU) and Canberra Health Services, focuses on MYC-driven cancers (搜索) and is funded by the Medical Research Future Fund (MRFF).
The trial will test PMR-116, an experimental anti-cancer drug developed by Professor Ross Hannan's team at ANU in collaboration with drug company Pimera Therapeutics (搜索). This innovative approach targets multiple cancer types including prostate, breast, ovarian, and haematological cancers (搜索), all unified by their dependence on the MYC protein (搜索).
Addressing the 'Undruggable' Challenge
The MYC protein (搜索) serves as a key regulator of cell growth and is implicated in approximately 70% of all cancers, according to Professor Mark Polizzotto, the haematologist leading the clinical trial. "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," Professor Polizzotto explained.
The challenge in targeting MYC directly stems from its disordered structure, as noted by Dr Nadine Hein, who has been leading the preclinical work on PMR-116 at ANU. "MYC has been the focus of cancer research for a long time, and it's challenging to target MYC directly as it has disordered structure," she said.
Novel Mechanism of Action
PMR-116 represents a breakthrough approach by targeting a pathway downstream of the MYC protein (搜索) rather than attempting to drug MYC directly. Professor Ross Hannan, ANU Centenary Chaired Professor in Cancer Biology, explained the drug's mechanism: "PMR-116 targets MYC-driven cancers (搜索) by inhibiting an enzyme to disrupt ribosomal biogenesis (搜索) – a crucial process hijacked in these cancers."
Dr Hein emphasized the significance of this indirect approach: "But by blocking this critical pathway downstream of MYC, we're now seeing remarkable results in cancers where MYC is involved." The drug has demonstrated promising results across various cancer types in preclinical studies.
Innovative Trial Design
The study employs a "basket trial" design, an efficient approach that groups patients based on the molecular driver of their cancer rather than the specific cancer type. This design allows researchers to study multiple cancer types simultaneously, as Professor Polizzotto noted: "The trial aims to address unmet clinical needs in difficult-to-treat cancers, and its design is efficient, saving time and resources compared to having separate trials for each cancer type."
Patient eligibility will be determined through MYC testing, with enrollment open to those whose standard treatments have stopped working and whose cancers show MYC involvement.
Multi-Center Collaboration
The clinical trial will be conducted across major Australian cancer centers, including the Canberra Hospital (搜索), Peter MacCallum Cancer Centre (搜索) in Victoria, and St Vincent's Hospital (搜索) in Sydney. The MRFF grant supports collaborative work across the Australian Capital Territory, New South Wales, and Victoria.
"Our team at ANU will coordinate the clinical trial, in partnership with clinicians at major cancer centres across Australia," Professor Polizzotto said. "Our goal with this trial is to target a key driver of cancer, and speed development to get effective treatments to patients sooner."
The trial represents a significant step forward in addressing one of oncology's most challenging targets, potentially opening new therapeutic avenues for patients with aggressive, MYC-driven cancers (搜索) that have historically had limited treatment options.