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Triple negative breast cancer (TNBC) is a more aggressive type of breast cancer.
TNBC's estrogen receptor, progesterone receptor and type 2 human epithelial growth factor receptor are all negative, which means that routinely can target these Receptor-acting therapies are difficult to work
.
However, researchers in Singapore have found a potential method for TNBC, and they found that the opportunity for treatment lies in appropriately changing the state of cancer cells
.
Although cancer cells have strong proliferation and invasion capabilities, they will switch between different cell states, such as changing from a less aggressive state (epithelial type) to a highly aggressive state (mesenchymal type).
Also known as epithelial-mesenchymal transition (EMT)
.
The researchers are thinking about reversing this process and realizing the mesenchymal-epithelial transition (MET), transforming cancer cells from strong to weak, so that the corresponding therapies can penetrate them
.
This is easier than developing new drugs and can increase the effectiveness of the therapy
To this end, a study in "Science-Progress" constructed a small molecule library to screen for compounds that promote the MET process
.
Among more than 2700 compounds, retinoids showed the best MET-inducing effect
▲The change in the status of cancer cells may become the key to the action of chemotherapy drugs (picture source: reference [2])
This shows that molecules related to retinoids may also play a role.
For example, bexarotene, a retinoic acid X receptor agonist, has shown excellent anti-cancer effects
.
In the test, the mesenchymal breast cancer cells treated with bexarotene showed a significant decrease in the ability to form tumor-like mammary glands, and the morphology of mesenchymal-like cells disappeared, showing the MET effect
In addition, MET caused by retinoids and bexarotene can make mesenchymal breast cancer cells lose their tumorigenicity
.
When the researchers transplanted breast cancer cells that had undergone MET changes into mice, the tumor growth volume was significantly smaller than that of the control group
For mice that have been transplanted with TNBC, the oral gavage method of bexarotene can significantly slow down the growth rate of the tumor, and the tumor burden is significantly reduced (compared with the control)
.
Through the detection of cancer cells, the researchers found that regardless of the cell state or gene expression pattern, breast cancer cells have already undergone the MET process
▲Bexarotene can slow down the growth of tumors in mice (picture source: reference [2])
At the same time, the researchers observed that after cancer cells have undergone bexarotene-induced MET, the interior of the cells will be filled with rich lipid droplets
.
This indicates that the processes related to the lipid metabolism of cancer cells may have been altered
And now with the occurrence of MET, fatty acids have not moved in the direction of decomposition, but have gradually been stored, which also indicates that the invasiveness of cancer cells has been reduced
Due to the optimistic results in animal experiments, the research team has launched a three-year human clinical trial to study the safety and effectiveness of bexarotene and chemotherapeutic drugs
Note: The original text has been deleted
Reference materials:
[1] Team discovers novel strategy to tameaggressive breast cancer and starts clinical trial.
[2] Loo SY, Toh LP, Xie WH, et al.
