The return of cyclophosphamide
The combination of drugs stopped the most aggressive lung cancer
Svetlana Maslova, Hi-tech+
Scientists used an already available chemotherapeutic drug, the effectiveness of which was dramatically increased by the discovery of a new cancer signaling pathway. Impressive preclinical studies that have stopped the development of cancer in all model animals allow us to start testing a new strategy in humans in the very near future.
Small cell lung cancer is one of the most aggressive forms of lung tumors with a very unfavorable prognosis. Platinum-based chemotherapeutic treatment can prolong the patient's life by an average of six months. Previously, this type of tumor was treated with cyclophosphamide, but it, along with platinum preparations, quickly provokes cancer resistance, so the life expectancy of patients is rarely prolonged.
In search of a solution to the problem, scientists began to look for ways to reduce tumor resistance in order to increase the effectiveness of existing drugs. Unlike the creation of new drugs, such a strategy can provide therapy options much faster. The results of their work are reported on the website of Washington University in St. Louis.
Scientists turned to already known biomarkers that had previously demonstrated a link with small cell cancer. For example, the association of the RNF113A protein is known in this regard, but its exact role has not yet been established.
New experiments have shown that RNF113A is regulated by the SMYD3 protein, the expression of which is greatly increased in small cell carcinoma and some other types of tumors. On the contrary, there is no excess of SMYD3 in a healthy body. In mouse models, scientists used the SMYD3 inhibitor and evaluated its effect separately and in combination with cyclophosphamide.
The combination of drugs quickly stopped the growth of the tumor without signs of further progression throughout the observation period.
Tumors (yellow) penetrate into the lungs of mice genetically predisposed to small cell lung cancer (left). Treatment of such mice with a chemotherapeutic drug and blocking resistance leads to the fact that the tumors practically disappear (right).
These results open up great prospects for patients with small cell carcinoma, the authors emphasized. They are already preparing to launch the first phase of clinical trials in the hope that the results will convince doctors to reconsider their attitude to the previously ineffective cyclophosphamide.
Article by Lukinović et al. SMYD3 impedes small cell lung cancer sensitivity to alkylation damage through RNF113A methylation-phosphorylation crosstalk published in the journal Cancer Discovery – VM.
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