[HTML][HTML] Inhibition of CXCR4–CXCL12 chemotaxis in melanoma by AMD11070
G O'Boyle, I Swidenbank, H Marshall, CE Barker… - British journal of …, 2013 - nature.com
G O'Boyle, I Swidenbank, H Marshall, CE Barker, J Armstrong, SA White, SP Fricker…
British journal of cancer, 2013•nature.comBackground: Despite intensive research and novel adjuvant therapies, there is currently no
cure for metastatic melanoma. The chemokine receptor CXCR4 controls metastasis to sites
such as the liver; however, the therapeutic blockade with the existing agents has proven
difficult. Methods: AMD11070, a novel orally bioavailable inhibitor of CXCR4, was tested for
its ability to inhibit the migration of melanoma cells compared with the commonly described
antagonist AMD3100. Results: AMD11070 abrogated melanoma cell migration and was …
cure for metastatic melanoma. The chemokine receptor CXCR4 controls metastasis to sites
such as the liver; however, the therapeutic blockade with the existing agents has proven
difficult. Methods: AMD11070, a novel orally bioavailable inhibitor of CXCR4, was tested for
its ability to inhibit the migration of melanoma cells compared with the commonly described
antagonist AMD3100. Results: AMD11070 abrogated melanoma cell migration and was …
Abstract
Background:
Despite intensive research and novel adjuvant therapies, there is currently no cure for metastatic melanoma. The chemokine receptor CXCR4 controls metastasis to sites such as the liver; however, the therapeutic blockade with the existing agents has proven difficult.
Methods:
AMD11070, a novel orally bioavailable inhibitor of CXCR4, was tested for its ability to inhibit the migration of melanoma cells compared with the commonly described antagonist AMD3100.
Results:
AMD11070 abrogated melanoma cell migration and was significantly more effective than AMD3100. Importantly for the clinical context, the expression of B-RAF-V600E did not the affect the sensitivity of AMD11070.
Conclusion:
Liver-resident myofibroblasts excrete CXCL12, which is able to promote the migration of CXCR4-expressing tumour cells from the blood into the liver. Blockade of this axis by AMD11070 thus represents a novel therapeutic strategy for both B-RAF wild-type and mutated melanomas.
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