New chemotherapeutic agent shows remarkable efficacy against multiple tumor types

A research team led by the Medical University of Vienna, the HUN-REN Research Centre for Natural Sciences and the Eötvös Loránd University in Budapest has developed a groundbreaking new chemotherapeutic agent, LiPyDau, which shows remarkable efficacy against multiple tumor types in preclinical studies. Published in the leading journal Molecular Cancer, the study introduces a highly promising strategy for tackling drug-resistant cancers.

Chemotherapy remains a cornerstone of cancer treatment despite well-known challenges, including toxic side effects and drug resistance. The research team led by Gergely Szakács from the Center for Cancer Research at MedUni Vienna, has been investigating drug resistance mechanisms and exploring ways to overcome them. The researchers synthetized a highly potent new derivative of anthracycline, a class of chemotherapeutic agents that has been central to cancer therapy for decades. The new compound, a chemically modified form of daunorubicin, proved too toxic for direct administration. To overcome this, it was encapsulated in tiny carrier vesicles called liposomes, creating LiPyDau. This liposomal formulation delivers the active ingredient directly to tumor cells while minimizing damage to healthy tissues. In mouse models of various cancers, LiPyDau dramatically reduced tumor burden and, in some instances, completely eliminated them.

Unique mechanism causes tumor cells to die

In preclinical studies, a single dose of LiPyDau almost completely inhibited tumor growth in a melanoma model. In lung cancer, the treatment was effective in both a standard mouse model and a model with human tumor cells that did not respond to common drugs. In aggressive mouse breast cancer models, LiPyDau treatment led to a near-complete tumor regression. Remarkably, in hereditary, difficult-to-treat forms of breast cancer, tumors were permanently eliminated. LiPyDau also showed promising activity against multi-drug resistant tumor cells. LiPyDau's exceptional efficacy is driven by a unique mechanism: it irreversibly links the two strands of DNA in cancer cells, causing damage that the tumor cells can no longer repair, ultimately leading to their death.

Anthracyclines, such as daunorubicin, are among the most widely used chemotherapeutic agents worldwide and are included on the World Health Organisation (WHO) list of essential medicines. However, their clinical effectiveness is often limited by toxic side effects and the development of resistance. Liposomal formulations – i.e. encapsulation of the active ingredient in nanoscale fat vesicles – have long been explored to reduce these limitations. "Our studies in mouse models show that encapsulating 2-pyrrolino-daunorubicin in liposomes enables the safe use of an otherwise too toxic, yet extremely potent new drug. The next important step is to conduct further studies to determine whether these promising results can be translated into clinical applications," says study leader Gergely Szakács.