Race Oncology (ASX:RAC) has announced the discovery of the primary mechanism of action of its lead anticancer candidate, (E,E)-bisantrene (RCDS1).
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New research from Race Oncology shows RCDS1 works by binding to and stabilising DNA and RNA G-quadruplex structures (G4s), rather than functioning like traditional chemotherapies such as doxorubicin.
The discovery is the result of collaborative scientific studies undertaken by Race and its partners. According to the company, stabilisation of G4-DNA and RNA impacts multiple cancer-driving pathways. This includes reducing the activity of oncogenes such as MYC, a master regulator implicated in over 70% of human cancers.
Additional effects include inhibiting the enzymes topoisomerase two and telomerase, as well as indirectly increasing levels of m6A RNA, which influences cancer cell growth and therapy resistance.
Race Oncology noted this finding marks a shift in understanding how RCDS1 functions. “The discovery (E,E)-bisantrene acts primarily by binding to G4-DNA and RNA structures, and not like the chemotherapeutic doxorubicin, fundamentally changes our thinking on how to best use this drug in the clinic,” said Race’s CEO, Dr Daniel Tillett.
Historically, bisantrene was assumed to act as a DNA-targeting chemotherapy similar to anthracyclines. However, Race’s studies using modern molecular profiling demonstrated that RCDS1 did not cluster with anthracyclines but instead aligned with G4-binding agents, such as actinomycin D. These insights prompted further exploration, leading to confirmation of G4-binding as its primary mechanism.
The company outlined several potential clinical and commercial benefits of the discovery. Identifying RCDS1’s mechanism of action enables more targeted selection of cancer types and drug combinations for development, potentially improving trial design and regulatory submissions.
Furthermore, Race highlighted this knowledge increases the likelihood of identifying predictive biomarkers, which may enhance regulatory approval prospects.
Race Oncology also emphasised that large pharmaceutical partners often require a clear mechanistic understanding of drug candidates, meaning the discovery could improve prospects for future partnerships.
Next steps for Race include additional preclinical studies to explore G4-DNA and RNA binding effects, determining the most relevant cancer indications for clinical trials, and evaluating potential drug combinations. The company also plans to publish its findings in peer-reviewed journals and present at international conferences.
To talk about the discovery, Race is hosting a webinar on October 8, at 6pm.
RAC shares have been $3.11.
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