Race Oncology Identifies Breakthrough Anticancer Mechanism for Bisantrene (RCDS1)

Race Oncology (ASX: RAC) has discovered the primary anticancer mechanism of action for its lead drug candidate (E,E)-bisantrene, also known as RCDS1.

New studies show the compound acts by binding to special DNA and RNA structures called G-quadruplexes, or G4s, which regulate many cancer-driving genes including the master switch MYC.

Chief executive officer Dr Daniel Tillett said the discovery reshapes how the company views the clinical use of bisantrene and opens new opportunities for both development and partnerships.

Reframing a Long-Standing Cancer Drug

Scientists first developed bisantrene in the 1970s and assumed it acted like older chemotherapy drugs such as doxorubicin.

The compound showed less toxicity to the heart than anthracyclines but its exact action remained unclear when clinical development stalled in the 1980s.

Race Oncology revived interest in the drug and launched a modern program to uncover its mechanism.

By testing RCDS1 against hundreds of cancer cell lines and comparing responses with known medicines, the team found it did not behave like doxorubicin but aligned instead with drugs that bind to G4 structures.

Further work confirmed that RCDS1 stabilises G4-DNA and RNA sites, shutting down the activity of oncogenes like MYC, inhibiting enzymes such as telomerase and topoisomerase 2, and indirectly increasing m6A levels in RNA—effects known to slow cancer growth and reduce resistance.

Targeting the Critical MYC Pathway

The MYC gene, which acts as a master controller of cell growth, division, and metabolism, is abnormally activated in more than 70% of human cancers and has long been seen as “undruggable” because its protein structure lacks binding sites for conventional drugs.

By binding to the G4 structure within the MYC promoter region, RCDS1 reduces MYC activity and weakens the signals that drive cancer cell proliferation.

Race researchers have shown that treatment with RCDS1 leads to strong downregulation of MYC across several cancer models.

This indirect but powerful control of MYC gives bisantrene a unique position in oncology, offering a way to hit a target long out of reach for the pharmaceutical industry.

Implications for Clinical Development

Dr Tillett said the discovery changes how Race will prioritise trials and design its drug combinations.

“Knowing that bisantrene acts through G4 binding rather than as an anthracycline-like drug fundamentally changes our thinking on how best to use this drug in the clinic,” he said.

“Bisantrene continues to surprise, and we look forward to building on this discovery in our future clinical and commercial plans.”

Understanding the mechanism also improves the chances of regulatory approval and pharma partnerships—large pharmaceutical companies want to see clear evidence of how drugs work, and regulators often require mechanistic data to predict side effects and identify patient groups most likely to benefit.

Race said the knowledge enables it to explore biomarker tests that predict patient response, potentially doubling the likelihood of regulatory success compared with drugs lacking such tests.

Additional Preclinical Studies

The company plans additional preclinical studies to explore how G4 binding affects cancer resistance and to pinpoint the cancer types most likely to benefit from RCDS1.

It also aims to investigate the best drug combinations to pursue in future trials.

Management said it will publish the findings in peer-reviewed journals and present data at international conferences, including an update on bisantrene’s heart-protective properties at the upcoming European Society of Medical Oncology meeting.

Race expects the discovery to accelerate discussions with potential partners and strengthen the case for advancing RC220 – its proprietary formulation of bisantrene – into late-stage clinical development.