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New strategies in dual/multi-integrin antagonism to target cancer metastasis

Summary of Project:

Background

The integrins are a family of transmembrane receptors which mediate cell-cell and cell-ECM adhesion, and signalling across the cell membrane involved in pathways controlling cell migration, proliferation, differentiation, cell survival and apoptosis. In cancers, their vital role in the cross-talk between the cell and extracellular matrix enhances the growth, migration, invasion and metastasis of cancer cells. The RGD-binding subfamily of integrins, comprising αvβ1, αvβ3, αvβ5, αvβ6, αvβ8, α5β1, α8β1, and αIIbβ3, are of particular interest, since there is strong evidence that their upregulation or ectopic expression on tumour tissues is correlated with tumour progression, treatment resistance, and a cancer stem cell phenotype.

Research areas currently under investigation include:

  • Development and characterisation of dual/multi-integrin antagonists for the treatment of advanced/metastatic cancers, particularly metastatic prostate cancer and malignant melanoma
  • Development of personalised anti-integrin agents: Identification of the optimum combination of integrins to target for effective treatment of a particular tumour
  • Investigation of multi-integrin antagonists targeting the prostate cancer stem cell niche: Identification of appropriate integrin combinations, and characterisation of new biological models and potential therapeutics
  • Investigation of combination therapies to combat integrin-mediated resistance to existing anticancer agents

Projects typically involve identification of integrin expression on cell lines and tissue samples, the development and characterisation of novel models to measure functional integrin inhibition, and/or investigation of the effects of integrin antagonists on cell survival, behaviour, and signalling.

Entry requirements:

At least 2:1 Honours degree in a relevant subject (preferably molecular biology, biochemistry, cancer biology etc)

Funding

Applicants will be expected to provide their own funding or external sponsorship. A bench fee of £10,000 will be applicable to this project, in addition to the tuition fees.

Supervisors:

Title and name:
Dr Helen Sheldrake
Position:
Lecturer in Organic and Medicinal Chemistry
Email address:
Telephone number :
Work+44 (0) 1274 236858
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