Breast cancer gene holds key to personalised medicine and new drug development

Nottingham scientists have identified a new breast cancer gene which, when over-expressed or mutated, indicates which patients will benefit from chemotherapy.

Camera icon
The study examined the expression of SPAG5 in more than 10,000 breast cancer samples

Nottingham scientists have identified a new breast cancer gene which, when over-expressed or mutated, indicates which patients will benefit from chemotherapy.

The collaborative study – involving Nottingham University Hospitals NHS Trust, Nottingham Trent University and the University of Nottingham – is published in the journal Lancet Oncology .

The team, funded by the Nottingham Hospitals Charity and the John and Lucille van Geest Foundation, says the SPAG5 gene has the potential to provide a new targeted therapy for breast cancer treatment and to tailor treatment to the patient's tumour for the best chance of a good response.

Almost 1.7 million women are diagnosed with breast cancer worldwide each year, with more than half a million dying of the disease. 'Oestrogen receptor negative breast cancer' accounts for almost a third of all patients.

The study examined the expression of SPAG5 in more than 10,000 breast cancer samples donated by patients.

The scientists found that oestrogen receptor negative patients with SPAG5 positive tumours – who underwent surgery and anthracycline chemotherapy – were 60% more likely to be cured, compared to patients in this group who received no chemotherapy treatment.

Importantly, all of the oestrogen receptor negative, SPAG5 negative cases, were found to do the same as the SPAG5 positive patients who received no chemotherapy.

The fact that the treatment did not impact the outcome in the SPAG5 negative cases suggests that SPAG5 is a good indicator of treatment response to anthracycline  - one of the most commonly used first line chemotherapy agents for oestrogen receptor negative breast cancer.

Research at Nottingham Trent University originally identified SPAG5 as an important molecule.

Professor Graham Ball, Nottingham Trent University


The work involved using machine-learning computer-based approaches to analyse the gene expression levels in more than 2,000 breast cancer genomes.

The approach identified candidate genes from the 48,000 in each genome. From these only 30 were selected for further study – the most significant of which was SPAG5. The importance of SPAG5 was validated in a further study of 8,000 breast cancer cases.

Graham Ball, Professor of Bioinformatics in Nottingham Trent University's John van Geest Cancer Research Centre, and a lead researcher on the study, said: "Research at Nottingham Trent University originally identified SPAG5 as an important molecule. Now we have shown that it is amplified in specific subtypes of breast cancer and that the gene and its associated protein are linked to a better outcome for patients and a better response to chemotherapy.

"This may mean that SPAG5 can be a new therapeutic target and a biological marker for the tailoring of breast cancer treatment and development of new therapeutics."

Professor Stephen Chan, consultant oncologist at Nottingham City Hospitals NHS Trust and a visiting professor at Nottingham Trent University, added: "SPAG5 is a marker of how fast the tumour is growing and how aggressive it is.

"When we looked back at data from patients who received treatment in the past, before anthracycline was in use, cases with high levels of SPAG5 did worst. Our research suggests such cases would have benefited from anthracycline chemotherapy.

"We are designing a clinical trial to use SPAG5 to select the best treatment for individual patients; it's all about personalised medicine.

"Our research is building towards this goal. With the continued support of the Nottingham Hospitals Charity and all the donors and fundraisers that continue to contribute to this effort, we will get there."

The research – an international collaborative effort led by Dr Tarek Abdel-Fatah, a research fellow in Professor Chan's group – also involved the University of Auckland, University of Cambridge, China's Northeast Normal University and Cancer Research UK.

We are designing a clinical trial to use SPAG5 to select the best treatment for individual patients; it’s all about personalised medicine.

Professor Stephen Chan, Nottingham City Hospitals NHS Trust

  • Notes for editors

    Press enquiries please contact Dave Rogers, Head of Communications, on telephone +44 (0)115 848 8782, or via email.

    Nottingham Personalised Therapy Oncology Research Group

    The group is led by Professor Stephen Chan and is focused on developing:

    • Cancer markers singularly and in combination, that can be used to predict patient response to both chemotherapy and targeted treatments.
    • Cancer markers that can be developed as new drug targets.
    • Cancer immunology and cancer vaccines.

    For further information please contact Paul Moseley via email.

    Nottingham Hospitals Charity

    Professor Chan’s research group has been supported by the Nottingham Hospitals Charity since 2010. It is thanks to the generous donations of dedicated fundraises that this work has been made possible.

    Telephone: 0115 962 7905

    Email

    Nottingham Trent University – John van Geest Cancer Research Centre

    Nottingham Trent University’s John van Geest Cancer Research Centre is a unique purpose-built scientific facility. Its aim is to save lives and speed recovery by improving the early diagnosis and treatment of cancer.
    The centre focuses on two key approaches to the treatment of patients with cancer:

    • Improving the diagnosis and management of breast and prostate cancers
    • Developing effective vaccines and immunotherapies that will significantly improve the survival rates and quality of life for cancer sufferers.

    Visit the John van Geest Cancer Research Centre website to find out more about its work, or to make a donation towards its vital scientific research.

    The Queen's Anniversary Prize for Higher and Further Education was awarded to Nottingham Trent University in November 2015. It is the highest national honour for a UK university and recognises the institution’s world-class research. Pioneering projects to improve weapons and explosives detection in luggage, enable safer production of powdered infant formula, and combat food fraud, led to the prestigious award.

Breast cancer gene holds key to personalised medicine and new drug development

Published on 15 June 2016
  • Category: Press office; Research; School of Science and Technology

Still need help?

+44 (0)115 941 8418