CXCR1 in breast cancer

Scientists from the University of Michigan and the INSERM (France) identified Cxcr1 gene as differentially expressed in cancer stem cells in comparison with other cancer cells in breast malignancies. CXCR1 is the receptor for interleukin 8 and has been involved in tumour progression and metastasis in several kinds of cancers, such as prostate, glioma, ovarian and breast cancers.

Furthermore, IL8 has been implicated in self renewal of stem cells in vitro. French researchers tested some small molecule inhibitors targeting CXCR1 or some antibody against this receptor in order to evaluate the effect on cellular behavior. These inhibitors directly acted versus cancer stem cells and at the same time indirectly induced cell death in bulk tumour. The promising result was that the whole cancer population was eliminated. A possible explanation for this larger effect could be the release of FAS ligand after inhibiting CXCR1 that determined apoptosis in all cancer cells. In animal model CXCR1 inhibitors reduced tumour mass and blocked metastasis, either alone or in combination with other drugs. Another possible approach to block cancer progression by acting on CXCR1 pathway is to interfere with IL8 production. Scientists from the University of Texas demonstrated that siRNA-IL8 reduced tumour weight in comparison to control in animal models. These studies seem really promising but further proof is necessary to validate CXCR1 pathway as a target for therapeutic intervention.

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