Promising drug target for aggressive ‘triple negative’ breast cancers identified …….December 2016

Scientists have identified a molecule crucial to the growth of triple negative breast cancers which they believe could now be targeted by drugs to help patients who are resistant to chemotherapy. ‘Triple negative’ means that the cancer cells lack the three receptors which are normally used to classify breast cancers: the oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This form of breast cancer therefore cannot be treated with targeted drugs commonly used to interfere with these receptors. These patients have less treatment options available typically only chemotherapy, surgery and radiotherapy.

When faced with chemotherapy, breast cancer cells suffer damage which triggers a signal inside the cell telling it to self-destruct. This process, known as apoptosis, is essential for chemotherapy to be effective. Researchers on this project have found that many triple negative breast cancers are often more aggressive because of the PIM1 molecule, which is usually broken down by chemotherapy,  is becoming resistant to the self-destruct signals which the chemotherapy gives out to affected molecules.

The team at Kings College London and the Institute of Cancer Research studied a total of 2,225 breast cancer patients, 319 of these had triple negative breast cancer. They found that the PIM1 molecule was increased in the majority of triple negative breast cancer compared to other subtypes.
By genetically depleting the production of PIM1 the researchers were able to reduce the growth of triple negative cells. By combining the PIM1 –inhibitor drug with chemotherapy this then led to an overall improvement in treating the triple negative cancer. Crucially, not only are PIM1-inhibitors already in development and being tested in clinical trials for blood cancers, but results from the trials suggest that they could be well-tolerated by patients.

Professor Andrew Tutt from King’s College London said:
“Many triple negative breast cancers are very resistant to chemotherapy and are ‘driven’ by genes that are very difficult to target with drugs. We have shown that PIM1, a molecule for which drugs are already in trials in other diseases, is so important for what makes a triple negative breast cancer cell malignant that they become addicted to it. It is early days but as PIM1-inhibitor drugs have already been discovered they may give us a new way to hit these cancer genes. The hope would be that these drugs could strip triple negative breast cancers of their defences so that they can be pushed over the cliff by other breast cancer treatments.”

To read more about this story please go to Breast Cancer Now or Nature Medicine Journal