Targeting Drug Resistance in BRCA-Related Cancers

BRCA1 and BRCA2 are tumour suppressor genes that play a crucial role in repairing damaged DNA. When either gene is altered due to a genetic or inherited mutation, this repair process is compromised, increasing the risk of several cancers, particularly breast, ovarian and prostate cancers.

PARP inhibitors have transformed treatment for people with BRCA‑mutant cancers. However, resistance remains a major challenge, with most patients eventually becoming resistant to PARP inhibitor therapy. Once resistance develops, treatment options become far more limited.

Researchers at the Ferrier Research Institute are committed to improving these outcomes. The team, led by Dr Farah Lamiable-Oulaidi and Professor Peter Tyler, is developing a new class of drugs designed to extend the effectiveness of PARP inhibitors. These new compounds target an enzyme called DNPH1. By blocking DNPH1, the drugs can re‑sensitise PARP inhibitor‑resistant cancers to treatment with PARP inhibitors. When used upfront in combination, this approach may also help prevent resistance from ever developing.

Translating science from the lab to the clinic

Farah, her team, and collaborators at the Albert Einstein College of Medicine have demonstrated in cell‑based studies that combining their DNPH1 inhibitors with PARP inhibitors can restore cancer cell sensitivity and cause cancer cell death. The next step is to move from preclinical cell‑based work into living systems. They are preparing to test the approach in animal models, providing crucial in vivo proof of concept, a key milestone on the path to the clinic.

The journey towards first‑in‑human trials remains long, but the foundations are being carefully put in place. What sets this project up for success is the approach to drug design and the researchers behind it. The team at the Ferrier Research Institute are world leaders in transition state analysis and the design of highly potent transition state analogue inhibitors. This approach allows the design of compounds with high selectivity and strong binding affinity to DNPH1, minimising off‑target effects while maximising potency.

The Ferrier Research Institute and its collaborators have a proven track record of translating chemistry into real‑world drugs. Professor Peter Tyler, a world‑class medicinal chemist at the Ferrier Research Institute, has discovered a drug that progressed all the way to market. Dr Farah Lamiable-Oulaidi, a Senior Scientist at the Ferrier Research Institute and KiwiNet Emerging Innovator, is the project’s science lead, driving the research towards clinical trials.

Wellington UniVentures has been instrumental in protecting and positioning this technology for real‑world use. This includes navigating intellectual property protection for the novel compounds, engaging with potential partners, and guiding researchers on the technical data package needed to progress commercial conversations. The team is now seeking pharmaceutical partners, investors, and clinical collaborators to help advance the technology through preclinical development and clinical trials.

“The number of patients this could be applicable to is significant and the impact would be immense,” said Sam Wojcik, Senior Commercialisation Manager, Wellington UniVentures. “By tackling PARP inhibitor resistance head‑on, this research has the potential to transform the prognosis of patients worldwide.”

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