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Targeting IL-1B to improve outcome for patients with breast cancer bone metastases.

  • Full or part time
  • Application Deadline
    Thursday, July 30, 2020
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Background: Breast cancer metastasis to bone is currently incurable. Treatment consists of combining anti-tumour therapies with bone strengthening agents such as zoledronic acid (ZA). Our research team found that administration of doxorubicin 24h before ZA increases the anti-tumour effect of either drug alone. When tested in patients, combining anti-tumour drugs with ZA increased survival in post-menopausal, but not in pre-menopausal, women.
We have new evidence that interleukin 1B (IL-1B) plays important roles in the spread of breast cancer to bone, especially in pre-menopausal women. Our data suggests that targeting IL-1B with clinically available drugs could stop breast cancer spreading and slow down, or reverse, bone metastasis. The clinical potential of novel combination therapies targeting IL-1B will be established in this project.

Aims:
1. Determine if neutralising IL-1B activity increases the anti-tumour effects of current standard of care for triple negative and ER+ve breast cancer metastasis.
2. Identify whether adding anti-IL-1B treatment to chemotherapy and ZA may provide therapeutic benefit for both pre-and post-menopausal women with breast cancer metastasis.
Methods: We will use syngeneic and human specific models of breast cancer PDX metastasis to human bone to investigate the effects of combining the anti-IL-1 treatment, Anakinra, with ZA and doxorubicin (ER-ve model) or tamoxifen (ER+ve model). These combination treatments will also be tested in laboratory models, mimicking pre- and post-menopausal conditions. Effects on tumour growth, subsequent metastasis and modulation of immune cells will be analysed to assess efficacy of these combination treatments and their translational potential into future clinical trials. Subsequent analysis of primary tumours, bone metastases and circulating tumour cells using ELISA, immunohistochemistry, flow cytometric and uCT techniques will be used to identify mechanisms by which these drugs exert their combined activity.

Impact: Comprehensive studies carried out during this PhD will establish whether IL-1B inhibition increases the anti-tumour effects of current standard of care. These data will pave the way for a clinical trial providing real potential for improved outcome for patients with metastatic breast cancer.

Funding Notes

Funding:
This is available as a self-funded project. In addition to fees and student living expenses, the work requires bench fee support of £15,000 per year.

Entry Requirements:
Candidates must have a first or upper second class honors degree or significant research experience.

References

Enquiries:
Interested candidates should in the first instance contact:

Dr Penelope Ottewell
Medical School
Beech Hill Road
Sheffield
S10 2RX

Tel: 0114 215 9058
Email: [email protected]

How to apply:
Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply

Please clearly state the prospective main supervisor in the respective box and select 'Oncology & Metabolism' as the department.

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