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

Terrance Lam, Chantel Mastos, Erica K. Sloan, Michelle L. Halls

Research output: Contribution to journalReview ArticleResearchpeer-review

1 Citation (Scopus)

Abstract

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 β2-adrenoceptor, have emerged as potential new therapeutic targets. Here, we describe how the β2-adrenoceptor accelerates TNBC progression in response to stress, and the unique signalling pathway activated by the β2-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.

Original languageEnglish
Article number108331
Number of pages14
JournalPharmacology & Therapeutics
Volume241
DOIs
Publication statusPublished - Jan 2023

Keywords

  • Compartmentalised signalling
  • G protein-coupled receptors
  • Intracellular receptors
  • Triple negative breast cancer

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