Pathological changes in GPCR signal organisation: Opportunities for targeted therapies for triple negative breast cancer

Triple negative breast cancer (TNBC) has the poorest prognosis compared to other breast cancer subtypes, due to a historical lack of targeted therapies and high rates of relapse. Greater insight into the components of signalling pathways in TNBC tumour cells has led to the clinical evaluation, and in some cases approval, of targeted therapies. In the last decade, G protein-coupled receptors, such as the 132-adrenoceptor, have emerged as potential new therapeutic targets. Here, we describe how the 132-adrenoceptor accelerates TNBC progression in response to stress, and the unique signalling pathway activated by the 132-adrenoceptor to drive the invasion of an aggressive TNBC tumour cell. We highlight evidence that supports an altered organisation of GPCRs in tumour cells, and suggests that activation of the same GPCR in a different cellular location can control unique cell responses. Finally, we speculate how the relocation of GPCRs to the wrong place in tumour cells presents opportunities to develop targeted anti-cancer GPCR drugs with greater efficacy and minimal adverse effects.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

Triple negative breast cancer (TNBC) has the worst prognosis among breast cancer subtypes. G protein-coupled receptors, particularly the β2-adrenoceptor, have been identified as potential therapeutic targets. In this study, we investigate how the β2-adrenoceptor promotes TNBC progression and triggers invasion in aggressive TNBC tumor cells. We also discuss the altered organization of GPCRs in tumor cells and the potential for developing targeted anti-cancer GPCR drugs.