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Dual CXCR4/CCR7 antagonists for the treatment of cancer

Summary of project:

Chemokines, particularly CXCL12, acting on CXCR4 receptor, and CCL19 and CCL21, acting on CCR7 receptor, have a multifaceted involvement in the regulation of various tumour cell functions, including growth, angiogenesis, survival, migration and immune evasion and in particular, play a critical role in the homing of tumour cells into metastatic target organs.

Recent evidence shows that CXCR4 and CCR7 are often co-expressed in cancers and this, compared to expression of either receptor alone, correlates to poorer prognosis and exacerbated metastasis in many cancers including breast, cervical, thyroid, and gastric. Hence there is a need to address both the CXCR4 and CCR7 axes and small molecule antagonism of both these receptors will presents a novel opportunity for cancer therapy.

This project builds on recent discoveries at ICT to demonstrate that small molecule CCR7 antagonists block lymphatic migration of tumour cells and used in tandem with CXCR4 antagonists significantly inhibit tumour growth, dissemination and metastasis.

Entry requirements:

At least 2.i Honours degree or equivalent.

Supervisors:

 

Title and name:
Dr Kamyar Afarinkia
Position:
Senior Lecturer in Medicinal Chemistry
Email address:
Telephone number :
Work+44 (0)1274 235831
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Title and name:
Dr Steve Shnyder
Position:
Senior Lecturer in Tumour Biology
Email address:
Telephone number :
Work+44 (0)1274 235898
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