New Method Identify Mechanism of Cancer Drugs in Depth

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Researchers from Francis Crick Institute developed a method to observe interaction of drugs with individual cancer cells in a tumor in real time.

Although chemotherapy is widely preferred treatment against various cancers, it fails to reach all cancer cells in a tumor. Current techniques used in cancer treatment are not capable of showing the exact cells targeted by a particular drug. This is due to the measurements taken from liquefied cancer biopsies. The major hurdle in these biopsies is that materials from different cells get mixed together. Now, researchers at the Francis Crick Institute and Imperial College London developed a new technique using a miniature fluorescent microscope, which measures and visualizes drug-target engagement of individual cells within in a tumor. The research was published in the journal Nature Communications on July 09, 2018 could help clinicians decide the best course and delivery of treatment for cancer patients.

The miniature fluorescent microscope mapped the chemotherapy drug doxorubicin that attacked ovarian cancer cells in living mice. The researchers observed significant variations in drug-target engagement between cells within a single tumor, and between different tumors. Furthermore, the drug-target engagement enhanced when doxorubicin was administered through abdominal injection instead of currently preferred intravenous methods. Previous mouse model showed that delivery of doxorubicin through blood does not reach all its target cells in the body. However, delivering the drug directly into the abdomen adjacent to ovarian tumors improved its target engagement. Moreover, the method was still insufficient in eliminating cancer cells. The new miniature fluorescent macroscopic mapping captures the interaction between two light-sensitive molecules. The DNA inside cancer cells with green fluorescent protein (GFP) are labeled. These GFP transfer energy to doxorubicin, which is intrinsically light-sensitive. The efficiency of this energy transfer is measured to determine the binding between the drug and DNA of different cancer cells in real-time. The research team stated that the technique is expected to be significantly effective with engineered biosensors that fluorescently tag cancer cells and can be used with combinations of other chemotherapy drugs.

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