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Promising approach to prevent the recurrence of breast cancer

The study provides important new insights into how breast cancer cells belonging to the HER2-positive subtype are able to awaken during treatment.

Thousands of lives could be saved as Japan begins to actively promote the HPV vaccine -- which can prevent cervical cancer -- after a decade of misinformation and weak policy left inoculation rates dismally low, advocates say
Thousands of lives could be saved as Japan begins to actively promote the HPV vaccine -- which can prevent cervical cancer -- after a decade of misinformation and weak policy left inoculation rates dismally low, advocates say - Copyright AFP Kazuhiro NOGI
Thousands of lives could be saved as Japan begins to actively promote the HPV vaccine -- which can prevent cervical cancer -- after a decade of misinformation and weak policy left inoculation rates dismally low, advocates say - Copyright AFP Kazuhiro NOGI

A proportion of breast cancers recur even after long periods without signs of cancer remaining dormant in the body. The reasons why dormant breast cancer cells awake even after several years are not well understood. Examining this, Finnish cancer researchers have discovered a mechanism that wakes up these dormant breast cancer cells.

The researchers demonstrated that preventing the mechanism can significantly improve treatment outcomes in experimental models. The study provides important new insights into how breast cancer cells belonging to the HER2-positive subtype are able to awaken during treatment.

The research group led by Jukka Westermarck, the Professor of Cancer Biology at the Turku Bioscience Centre, approached this research question by treating breast cancer cells sensitive to treatment with HER2 inhibitor for nine months and by monitoring how these cancer cells were able to restart their growth during the treatment.

By sequencing the molecular changes in the cells, Westermarck identified the DUSP6 protein, whose expression closely followed the development of therapy resistance. The researchers showed that when the activity of the Dual specificity phosphatase-6 (DUSP6) protein was blocked during cancer treatment, breast cancer cells lost their ability to grow.

Westermarck’s team also found that blocking the protein also made the previously treatment-resistant cancer cells more sensitive to HER2 inhibitors. Another important finding was that by inhibiting DUSP6, it was possible to slow the growth of breast cancer metastases in the brain in mouse models.

“Based on our findings, blocking the DUSP6 protein could therefore provide a basis for effective combination therapy also in HER2 breast cancer cases that have already lost response to treatment,” explains Westermarck.

The significance of the study is highlighted by access to experimental drug molecules that inhibit the DUSP6 protein. It was found that by administering the drug the protein could be inhibited in mice without significant side effects. Importantly, the drug was shown to significantly enhance the therapeutic effect of several existing HER2 inhibitors.

There is sufficient evidence that DUSP6 is a very promising target protein for future cancer drug development and worth investigating.

The research has been published in the journal EMBO Molecular Medicine, titled “DUSP6 inhibition overcomes Neuregulin/HER3-driven therapy resistance in HER2+ breast cancer.”

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Written By

Dr. Tim Sandle is Digital Journal's Editor-at-Large for science news. Tim specializes in science, technology, environmental, business, and health journalism. He is additionally a practising microbiologist; and an author. He is also interested in history, politics and current affairs.

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