Scientists have uncovered a previously unknown mechanism that helps breast cancer cells survive the intense stresses of being malignant, revealing a promising new target for future cancer therapies. 

A new study has shown that breast cancer cells become highly dependent on a cell membrane protein called GPR89 to manage stress inside the cell, allowing them to cope with the demands of rapid growth. 

These findings suggest that blocking GPR89 could offer a highly selective way to kill tumour cells while sparing healthy tissue. Importantly, they could also have implications for many other types of cancer driven by similar biological processes. 

Researchers at The Institute of Cancer Research (ICR), London, led the study, which was primarily funded by Breast Cancer Now. 

Potential for highly selective therapies 

Cancer development is often fuelled by oncogenes, which drive cells to grow and divide uncontrollably. One major source of this pressure occurs within the endoplasmic reticulum (ER), a specialised structure inside cells responsible for producing and processing proteins. When cells are pushed into overdrive by oncogenes, the ER can become overloaded, triggering a state known as ER stress. 

In breast cancer cells, the protein GPR89 functions as part of an adaptive response that enables cancer cells to cope with oncogene-induced ER stress. Importantly, the team’s experiments indicate that breast cancer cells become especially reliant on GPR89 once it is operating within the ER. This raises the possibility that drugs designed to block or inhibit the protein could selectively impair cancer cells while leaving normal cells relatively unaffected. 

Co-senior author Professor Andrew Tutt, Professor of Breast Oncology, Head of the Division of Breast Cancer Research and Director of the Breast Cancer Now Toby Robins Research Centre at ICR, said: “This work reveals an entirely new way in which cancer cells can gain the benefits of oncogene activation while controlling the harmful stress that those same oncogenes create. What is particularly exciting is that this adaptation appears to create a cancer-specific dependency on GPR89, opening up the possibility of developing highly selective therapies that target tumour cells.”