Race Oncology (ASX: RAC) has made a significant breakthrough in understanding how its lead cancer drug candidate bisantrene works, discovering a novel mechanism that could unlock treatment for previously "undruggable" cancer targets. The company's stock surged 23% following the announcement of research findings that reveal bisantrene's unique approach to targeting the MYC oncogene.
Revolutionary G-Quadruplex Targeting Mechanism
The research team discovered that bisantrene, also known as RCDS1, acts by binding to special DNA and RNA structures called G-quadruplexes (G4s). These 3D knots in genetic code regulate how certain cancer-driving genes are switched on or off. By stabilizing these G4 structures, bisantrene can effectively block the activity of cancer-promoting genes such as MYC, a well-known master regulator of cell growth.
"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," said Dr. Daniel Tillett, Race Oncology's chief executive officer. "Bisantrene continues to surprise, and we look forward to building on this discovery in our future clinical and commercial plans."
Addressing the MYC Challenge
The discovery is particularly significant because targeting MYC directly has been one of oncology's hardest challenges for decades. MYC is abnormally activated in more than 70% of human cancers and has long been considered "undruggable" because its protein structure lacks binding sites for conventional drugs. Under normal conditions, MYC supports healthy cell growth and replication, but in cancer, it can become overactive or mutate, driving uncontrolled tumor survival and expansion.
Race Oncology's approach offers a novel pathway to achieve what many have tried and failed to do—indirectly suppress MYC activity by stabilizing the G4 structures it depends on. The research confirmed that treatment with RCDS1 leads to strong downregulation of MYC across several cancer models, giving bisantrene a unique position in oncology.
From Historical Mystery to Modern Breakthrough
Scientists first developed bisantrene in the 1970s and initially assumed it acted like older chemotherapy drugs such as doxorubicin. The compound showed less toxicity to the heart than anthracyclines, but its exact mechanism 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 stabilizes 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.
Enhanced Development and Commercial Prospects
The discovery of bisantrene's precise mechanism of action significantly improves the drug's development outlook and commercial appeal. With this knowledge, researchers can now identify the cancer types most likely to respond and design effective drug combinations, avoiding the costly and time-consuming trial-and-error approach.
Regulators such as the FDA favor drugs with clearly defined mechanisms, as it improves predictability, enhances patient safety, and guides appropriate use. For large pharmaceutical companies, this clarity is particularly valuable, as understanding exactly how a drug works reduces scientific risk, strengthens trial design, and increases the likelihood of forming commercial partnerships.
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. Race also aims to investigate the best drug combinations to pursue in future trials and explore biomarker tests that predict patient response, potentially doubling the likelihood of regulatory success compared with drugs lacking such tests.
Management 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. The company 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.
