Aggressive breast cancer, new oral drug kills only tumor cells without toxic effects

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Aggressive breast cancer, new oral drug kills only tumor cells without toxic effects

Australian researchers have shown in laboratory tests that an experimental oral drug (called CDDD11-8) can selectively kill cells of triple-negative breast cancer, the most aggressive form of breast cancer. The molecule also breaks down cancer cells in sick mice and in organoids cultured from biopsies of patients with the tumor, sparing healthy cells. Hopes for a possible innovative therapy.

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Breast cancer cells before and after treatment. Credit: University of Adelaide

In laboratory tests, scientists have shown that a new experimental oral drug can kill triple-negative breast cancer cells while sparing healthy ones. Furthermore, it is also able to hunt for metastases , the cancerous cells that spread from the original tumor to other organs and tissues, the main cause of death of malignant tumors . Triple negative breast cancer (TNBC) is considered one of the most aggressive of all and to date there is no specific treatment . The reason is that it does not have the receptors of other breast cancers that are targeted by chemotherapy and immunotherapy .

Breast cancers are classified and treated based on positivity for hormone receptors (estrogen and progesterone) and for the HER2 protein , a receptor for epithelial growth factor. The triple negative, as the name suggests, does not have them and is therefore very difficult to attack. It also mainly affects young women and has the highest relapse and mortality rates within five years of diagnosis. In short, it is one of the most lethal forms of cancer and having discovered a very effective molecule (in preclinical tests, we reiterate) gives new hope for achieving an ad hoc therapy . But it will still take years before it becomes available, if it actually proves to be as safe and effective as the tests suggest.

An international research team led by scientists from the Adelaide School of Medicine at the University of Adelaide, who collaborated closely with colleagues from the Department, determined the effectiveness of the new oral drug against triple-negative breast cancer cells. of Drug Discovery and Development at the University of South Australia and the Department of Surgery and Cancer at Imperial College London. The researchers, coordinated by Professor Theresa E. Hickey of the “Dame Roma Mitchell” Cancer Research Laboratories at the Australian university, decided to test an experimental drug called CDDD11-8 for their experiments. It had been developed in 2022 by Professor Shudong Wang (co-author of the new study) for the treatment of acute myeloid leukemia , the blood cancer against which Sinisa Mihajlovic fought.

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This aggressive neoplasm spreads by exploiting a protein that experts call cyclin-dependent kinase 9 ( CDK9 ): the drug CDDD11-8 inhibits it selectively . Because experts believe that aggressive cancers that are highly dependent on transcription (a copying process involving RNA) such as triple-negative breast cancer can be fought precisely by targeting the CDK9 pathway, Professor Hickey's team decided to test it in the laboratory in various experiments. The results obtained, as indicated, were extremely promising.

In fact, the drug CDDD11-8, when administered on cultures of breast cancer cells, was able to rapidly block their growth and kill them, significantly reducing their number, as shown in the image at the top of the article. “It induced cell cycle arrest and increased apoptosis (so-called NDR cell suicide) of the cell lines,” the scientists explain in the study abstract. The drug was also tested on murine models (mice) with transplanted breast cancer and on human organoids generated with cells taken from biopsies of patients with the aggressive neoplasm. In both cases the tumor masses were reduced and above all no toxic side effects on healthy cells were observed . This is because, according to experts, cancer cells are much more dependent on the targeted CDK9 pathway. The drug was also able to effectively attack three organoids derived from metastatic breast cancer lesions .

“Our preclinical study shows that the drug was able to stop the multiplication of tumor cells, but did not affect normal cells in breast tissue taken from patients. It is still early days, but based on this initial evidence, we believe that inhibiting this protein could lead to a treatment for triple-negative breast cancer and that this new drug should be further developed,” Professor Hickey said in a press release. The hope is that the foundations may have truly been laid for an innovative treatment against triple-negative breast cancer. But as indicated, it will take years to reach this potential outcome. The details of the research “Selective inhibition of CDK9 in triple negative breast cancer” were published in the specialized scientific journal Oncogene of the Nature circuit.

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