Professor Steve Archibald S.J.Archibald@hull.ac.uk
Professor in Molecular Imaging
Novel dual CXCR4/CXCR7 receptor drugs: targeting secondary disease progression and resistance to immunotherapy in breast cancer
People Involved
Project Description
CXCR4/CXCR7-CXCL12 chemokine axis plays a pivotal role in breast cancer (BC) growth, survival, therapy evasion and metastasis. Clinically overexpression of CXCR4/CXCR7-CXCL12 correlates with aggressive BC disease and poor outcome. Evidence suggests cooperativity between CXCR4 and CXCR7 chemokine receptors
in governing the precise biological response to CXCL12 stimulation. This will limit the effectiveness of targeting either receptor independently. We have developed first-in-class dual inhibitors of CXCR4 and CXCR7. Pilot studies confirm efficacy against aggressive BC in-vivo. Dual inhibition of CXCR4 and CXCR7 could elicit
profound, pleiotropic anti-cancer effects providing a powerful new line of therapy for BC patients with high risk of progressive disease.
Aims
Aim 1: Evaluate impact of dual targeting of CXCR4/CXCR7 on BC phenotype, stem-cell modulation and
metastatic potential in-vitro
Aim 2: Establish impact of CXCR4/CXCR7 targeting on growth and metastatic progression of aggressive
human BC in-vivo
Aim 3: Establish cooperativity of CXCR4/CXCR7 targeting on the sensitivity of aggressive BC to
immunotherapy and changes to the tumour “landscape”
Aim 4: To probe inflammatory phenotype and stem cell modulation of aggressive human BC in response to dual CXCR4/CXCR7 targeting in-vivo
| Status | Project Complete |
|---|---|
| Value | £31,500.00 |
| Project Dates | Aug 1, 2019 - Jul 31, 2023 |
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