A promising new treatment to combat "undruggable" cancers has been green-lit for a human trial in 2025. It's hoped the novel drug will be able to stunt the growth and enable the effective treatment of cancers driven by the MYC oncogene and its MYC protein.
MYC codes for the MYC protein – one that fuels tumorigenisis (tumor growth) and drives both the development and spread of cancer and renders many tumor-supressing treatments ineffective. Its overexpression can be found in around a third of prostate, pancreatic, liver, gastric and breast cancers, and nearly two thirds of all ovarian cancers.
“Approximately 70% of all cancers are fueled by abnormal MYC activity,” said hematologist and ANU professor Mark Polizzotto. “MYC is one of the most notorious cancer-causing genes, and tumors driven by MYC overexpression are often among the most aggressive and difficult to treat."
The trial, which will begin later this year, will center around the anti-cancer drug PMR-116. Showing great promise in preclinical studies, PMR-116 disrupts a pathway downstream of MYC, inhibiting an enzyme that stunts the synthesis of ribosomal RNA (rRNA) – a process that's crucial in protein synthesis. By blocking the production of MYC, tumors are then vulnerable to attack.
The study – led by The Australian National University (ANU) and Canberra Health Services – will be a "basket trial," enrolling patients with different kinds of cancers – just ones that have the MYC driver fueling them.
“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," said Polizzotto. “MYC has long been considered ‘undruggable’, but early results of PMR-116 show promise in changing that perception."
In 2023, a study out of the The University of Melbourne found that mice treated with PMR-116 reduced the incidence of prostate cancer lesions by 85% over four weeks, and slowed the spread of MYC-driven cancer growth by 50% in just 12 hours – all within a short time of taking the drug.
“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,” said Dr Nadine Hein, who has been leading the pre-clinical work on PMR-116 at ANU. “Directly targeting MYC has long been a challenge."
PMR-116 is a novel drug developed by scientists at ANU and pharmaceutical company Pimera Therapeutics. It's not the first to target the MYC protein, but research is still ongoing.
"We are targeting dysregulated RNA polymerase I (Pol I) transcription in MYC-driven cancers," the company noted. "Pol I transcription of ribosomal RNA genes (rDNA) is tightly regulated downstream of oncogenic pathways, and its dysregulation is a common feature in cancer and other human diseases.
"Because the exclusive function of Pol I is the transcription of rRNA, which is the rate limiting step of ribosomal biogenesis, the inhibition of Pol I transcription presents a novel approach for therapeutic intervention using a biomarker-driven precision medicine strategy," it added.
The expansive trials will be conducted out of the Canberra Hospital, Peter MacCallum Cancer Centre in Victoria, and St Vincent’s Hospital in Sydney, among others.
“Our team at ANU will coordinate the clinical trial, in partnership with clinicians at major cancer centers across Australia,” said Polizzotto. “Patients with standard treatments that have stopped working will be tested for MYC and, if it is implicated in their cancer, will be eligible to enroll in the trial.
“Our goal with this trial is to target a key driver of cancer, and speed development to get effective treatments to patients sooner," he added. “But by blocking this critical pathway downstream of MYC, we’re now seeing remarkable results in cancers where MYC is involved.”
Source: The Australian National University