Killing cells while they sleep to stop the spread of breast cancer

23rd February 2022

Our researchers in Italy have uncovered a new mechanism that helps breast cancer cells to survive the effects of treatment once they have spread to other parts of the body. By targeting these cells while they "sleep" or lay dormant, the researchers hope that they will be able to identify ways to stop people with breast cancer progressing to an advanced stage of the disease.

Microscope image of a breast cancer cell grown in the lab

In the last 40 years, breast cancer survival has improved dramatically thanks to research that has led to ways to treat the disease. However, for many patients there is a risk that the disease comes back after successful treatment. When cancer does come back, it is often more aggressive and harder to treat.

One reason for this is that some cancer cells can escape the treatment and spread to many different sites in the body. Once there, the cells can enter a “sleep” state and remain dormant, until they wake up and cause the cancer to return. These sleeping cells are difficult to treat because they lack many of the characteristics of cancer cells and can’t be killed by chemotherapy.

This inability to completely eradicate cancer during treatment is a key challenge research needs to overcome if we are to develop effective treatments for all breast cancer patients. Dr Sirio Dupont from the University of Padua in Italy and his team recently discovered that cancer cells migrate from the breast, which is made of more rigid tissue, to the tissues that are softer, such as lungs. It seems that the “softness” of these tissues can help cancer cells survive in a dormant state.

 

Sirio Dupont Dr Sirio Dupont

As the researchers started looking more closely at why these soft tissues help the migratory cancer cells to survive, they uncovered a remarkable mechanism. The team found that healthy cells in the softer tissues release more antioxidants - chemicals that are produced by the body and protect the organism from damage. Surprisingly, they found that the increase in antioxidants creates a favourable environment for the arriving cancer cells and this makes them difficult to kill with chemotherapy.

Looking at this in more detail, the research team found that specific molecules, called DRP1 and NRF2, were responsible for triggering antioxidant release depending on how stiff or soft the tissue is. The researcher believe that this finding suggests that blocking DRP1 and NRF2 could be a way to target dormant cancer cells that have spread to other parts of the body, making them treatable with chemotherapy.

Sirio Dupont Dr Sirio Dupont
Our hope is that these findings can be translated into a real drug treatment that can be administered to patients to kill “sleeping” cancer cells before they awake into full-blown metastases. If the approach that we propose is feasible, this could prevent disease relapse and prolong survival of people with cancer.

Breast cancer breakthroughs like Dr Dupont’s are incredibly exciting because they mark the beginning of a journey towards new treatments that could stop the development of secondary or metastatic breast cancer. This stage of the disease is responsible for all the deaths from breast cancer so this research could help save the lives of many people in the future.

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