KINETO Lab announcing that research about how safe delivery of a highly toxic anthracycline derivative through liposomal nanoformulation achieves complete cancer regression, was published in Molecular Cancer journal. In this study, where was used our patient-derived tumor xenograft (PDTX) model of invasive lung adenocarcinoma, it was developed LiPyDau therapeutic with promising and highly effective therapeutic approach for combating drug resistant cancer and potential use in the clinic.

The results of this study had a huge reflections from the scientific and non-scientific audience, in Hungary, Austria and worldwide. Attila Kigyós, the founder and CEO of KINETO Lab, which participated in the research, says for Telex.hu that this drug is by far the most effective anti-tumor compound ever tested, and he believes that they must do everything they can to develop it to a level where clinical trials are possible, or where it will attract the interest of a large pharmaceutical company enough to buy it and develop it into an oncology product. “LiPyDau has a serious chance of becoming one of the Hungarian-developed cancer drugs,” added the head of the development company.

Chemotherapy remains the cornerstone of cancer treatment despite its well-documented challenges, including toxic side effects and drug resistance. Here, we demonstrate that a novel, highly toxic, daunosamine-modified derivative of daunorubicin (2-pyrrolino-daunorubicin, PyDau) can be safely administered to mice when encapsulated in liposome.

PyDau was synthesized from daunorubicin in a one-step reaction. Its increased in vitro cytotoxicity was confirmed across 42 human cell lines representing 12 cancer types, including multidrug resistant cells. The activity profile of this new derivative was analyzed in the context of 13 commonly used cancer drugs across a panel of lymphoblast cell lines missing individual components of DNA-repair enzymes. To enable in vivo application, PyDau was encapsulated in pegylated liposome, resulting in liposomal PyDau (LiPyDau). In vivo efficacy of LiPyDau was evaluated in three allograft models (melanoma, breast, lung), a xenograft model (uterine sarcoma), a patient-derived xenograft model (lung), and a genetically engineered mouse model of mammary cancer, including two models of drug resistance.

While PyDau exhibited up to 1000-fold greater cytotoxicity than daunomycin and doxorubicin against cancer cell lines, its in vivo application was hindered by an extremely narrow therapeutic window. Liposomal nanoformulation mitigated the limiting toxicity, allowing LiPyDau to be tested in preclinical allograft and xenograft mouse models. LiPyDau demonstrated robust efficacy across all models including multidrug-resistant cancer, completely eradicating tumors in a genetically engineered mouse model of triple-negative breast cancer. LiPyDau exerts its anticancer effect through a unique mechanism involving the crosslinking of complementary DNA strands, resulting in irreversible DNA damage.

Liposomal formulations of extremely cytotoxic anthracycline analogs, such as LiPyDau, represent a promising and highly effective therapeutic approach for combating drug resistant cancer.

The publication can be accessed under the following link.