Exploring the role of ADRB2 in triple negative breast cancer

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https://research.brighton.ac.uk/en/projects/to-determine-how-polymorphisms-in-the-stress-hormone-receptor-adr

established December 2023

 

 

Triple negative breast cancer (TBNC) accounts for approximately 20 per cent of breast cancer subtypes. It is characterised by the absence of three receptors:

  • oestrogen receptors
  • progesterone receptors
  • human epidermal growth factor receptor 2 (HER2).

Women with TNBC have lower survival rates with an increased rate of recurrence. We have shown that stress hormones (noradrenaline [NA]) at physiological concentrations, through activation of beta adrenergic receptor ADRB2, decrease the efficacy of chemotherapy by interfering with the cell cycle.

It is known that prolonged stress hormone binding leads to receptor de-sensitisation, however, gene variants in ADRB2 reduce receptor desensitization leading to potential increased ADRB2 activation.

We propose that single nucleotide polymorphisms (SNPs) within the genes that encode ADRB2 could result in a decreased therapeutic response which may translate to shorter recurrence-free survival.

Team Verrico have provided funding for this study.

Team-verrico-logo

Project timeframe

This project commenced in November 2017. New funding has extended the project for the period June 2018 to June 2019.

Project aims

The aims of this research project are to:

  • determine the frequency of ADRB2 (codons 16 and 27) polymorphic alleles in 60 breast tissues from patients with TNBC to estimate an effect on survival.
  • expand study numbers using philanthropic funding to calculate the relative risk these genetic polymorphisms impose on survival.
  • corroborate ADRB2 polymorphism frequencies from the experimental cohort (Breast Cancer Now tissue bank) with a validation cohort sourced from the Welsh Health Partners Biobank, London.
  • confirm the presence of ADRB2 receptor expression in relation to genotype.

Project findings and impact

This project is ongoing; output, findings and impact will be updated in due course.

Research team

Dr Melanie Flint
Dr Caroline Garrett
Dr Greg Scutt

Output

Output will be updated in due course.

Partners

, SHORE-C
Dr Gargi Patel, BSUH
Dr Stephen Bremner, Brighton and Sussex Clinical Trials Unit