Groundbreaking Trial for “Undruggable” Cancer Target Set to Begin

A breakthrough cancer therapy aimed at treating so-called “undruggable” cancers is scheduled to enter human trials in 2025. This innovative treatment targets tumors driven by the MYC oncogene and its associated protein, with the goal of slowing tumor growth and improving treatment outcomes.

The Role of the MYC Oncogene in Cancer Progression

The MYC gene encodes a protein that plays a major role in promoting tumor development and spread, often making traditional cancer therapies ineffective. MYC overexpression is found in roughly one-third of prostate, pancreatic, liver, gastric, and breast cancers—and in nearly two-thirds of ovarian cancers.

Professor Mark Polizzotto, a hematologist at The Australian National University (ANU), explained that abnormal MYC activity drives nearly 70% of cancers.It’s one of the most well-known cancer-promoting genes, and tumors linked to it are typically aggressive and hard to treat.”

Set to launch later this year, the trial will investigate PMR-116, a drug that showed impressive results in preclinical models. PMR-116 targets a process downstream of MYC by blocking an enzyme vital to the creation of ribosomal RNA (rRNA), which is essential for protein production. This disruption weakens the cancer’s defenses by halting MYC’s activity, making tumors more susceptible to treatment.

A Broad Approach: Basket Trial Design

Led by ANU and Canberra Health Services, the study will use a “basket trial” design, recruiting patients with different types of MYC-driven cancers. This structure allows researchers to test one therapy across multiple cancer types, streamlining development and resource use.

Polizzotto said the trial aims to meet urgent clinical needs in cancers that are notoriously difficult to treat. He added that although researchers have long labeled MYC as ‘undruggable,’ early signs from PMR-116 are beginning to change that perception.

Earlier research from the University of Melbourne in 2023 revealed that PMR-116 reduced prostate cancer lesions in mice by 85% in four weeks, and slowed MYC-driven cancer spread by half in just 12 hours following treatment.

Dr. Nadine Hein, who leads preclinical research on PMR-116 at ANU, noted that researchers have focused on MYC in cancer biology for decades.Its irregular structure makes it tough to target directly, which is why our strategy works downstream instead.”

A Novel Mechanism: Inhibiting RNA Polymerase I

Scientists at ANU, in collaboration with biotech firm Pimera Therapeutics, developed PMR-116. While it’s not the first drug to focus on MYC, its approach is distinctive. The company explained that they are targeting abnormal RNA polymerase I (Pol I) activity in MYC-driven cancers. Since Pol I is solely responsible for rRNA transcription—an essential step in ribosome formation—disrupting this process could provide a precise and effective treatment strategy.

The clinical trials will take place across multiple Australian institutions, including Canberra Hospital, Peter MacCallum Cancer Centre in Victoria, and St Vincent’s Hospital in Sydney.

“Our ANU team will oversee the trial in coordination with clinicians from leading cancer centers around the country,” said Polizzotto.Clinicians will screen patients whose standard treatments have failed for MYC involvement, and they will enroll those who are eligible.

Polizzotto concluded, “Our mission is to directly confront a major cancer driver and bring new, effective therapies to patients as quickly as possible. By targeting a key downstream mechanism of MYC, we’re seeing exceptional results in cancers where MYC plays a central role.

Read the original article on: New Atlas

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