Targeting IL-8 signalling to inhibit breast cancer stem cell activity

Figures & data

Figure 1. Model of cytokine networks depicting the proposed interactions between cancer cells and stromal cells: production of IL-8 by cancer cells, mesenchymal cells and macrophages increases cancer stem cell activity via CXCR1/2 by triggering EGFR/HER2-dependent and -independent signalling pathways. Numbers in square brackets refer to relevant reference.

Table 1. Summary of clinical trials of IL-8 and CXCR1/2 targeting agents in breast cancer and other diseases.

Agent	Pharmaceutical company	Clinical trial	Description
Anti-IL-8 antibodies
ABX-IL8	Abgenix	NCT00035828 Phase II (completed)	Evaluate safety and efficacy in patients with chronic bronchitis and COPD
HuMax-IL8 (HuMax-Inflam/MDX-018)	Genmab A/S	Phase I/II (completed) [36]	Evaluate safety and efficacy in patients with palmoplantar pustulosis
Decoy protein
PA401 (IL-8 mutant)	ProtAffin Biotechnologie AG	NCT01627002 Phase I (active, not recruiting)	Assess safety, tolerability, immunogenicity and pharmacokinetics
Small molecule antagonists of CXCR1/2
GSK1325756	GlaxoSmithKline	NCT01209052 Phase I (completed)	Assess the safety, tolerability, pharmacokinetics and pharmacodynamics
GSK1325756	GlaxoSmithKline	NCT01209104 Phase I (completed)	Evaluate the food-effect and proton-pump inhibition on the pharmacokinetics and safety
GSK1325756	GlaxoSmithKline	NCT01453478 Phase I (completed)	Evaluate the relative bioavailability of different drug formulations during suppression of gastric acid secretion
AZD5069	AstraZeneca	NCT01480739 Phase I (completed)	Assess neutrophil number and function in peripheral blood
SCH 527123	Merck	NCT00688467 Phase II (completed)	Evaluate the efficacy and safety in subjects with allergen-induced asthma
Reparixin	Dompé spa	Phase Ib (recruiting) [44]	Assess effects in tumour growth in combination with standard chemotherapy in patients with HER-2 negative metastatic breast cancer
Reparixin	Dompé spa	NCT01861054 Phase II (recruiting)	Investigate safety and effects on CSCs in early breast cancer patients in the time period between clinical diagnosis and surgery
Reparixin	Dompé spa	NCT00224406 Phase II (completed)	Investigate safety and efficacy in the prevention of primary graft dysfunction after lung transplantation
Reparixin	Dompé spa	NCT00248040 Phase II (completed)	Assess safety and efficacy in the prevention of delayed graft function after kidney transplantation
Reparixin	Dompé spa	NCT01817959 Phase III (recruiting)	Assess safety and efficacy in the prevention of graft dysfunction after pancreatic islet transplantation
DF2156A	Dompé spa	NCT01571895 Phase II (terminated)	Evaluate safety and efficacy in patients with active bullous pemphigoid

Trials in breast cancer are highlighted in bold. Numbers in square brackets refer to relevant reference.

NCT: National clinical trial number; COPD: chronic obstructive pulmonary disease.

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