Translating an Antagonist of Chemokine Receptor CXCR4: From Bench to Bedside

Wong, Donald; Korz, Walter

doi:10.1158/1078-0432.ccr-07-4846

Cited by 170 publications

(136 citation statements)

References 55 publications

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“…29 In preclinical models, such treatments have been shown to be effective not only in decreasing metastasis from breast cancer, but also in inhibiting primary tumor growth in breast cancer. 5,6 As most breast cancers express at least moderate to high levels of CXCR4, 10,11,30 there is a risk that these therapeutic agents may not be adequately targeted, perhaps impeding their clinical development.…”

Section: Discussionmentioning

confidence: 99%

The Influence of Tumor-Host Interactions in the Stromal Cell-Derived Factor-1/CXCR4 Ligand/Receptor Axis in Determining Metastatic Risk in Breast Cancer

Hassan

Ferrario

Saragovi

et al. 2009

The American Journal of Pathology

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The chemokine stromal cell-derived factor-1 (SDF-1) may function to attract CXCR4-expressing cancer cells to metastatic organs. We have previously demonstrated that low plasma SDF-1, a host-derived marker, increases distant metastatic risk in breast cancer. We therefore hypothesized that tumors overexpressing the SDF-1 receptor CXCR4 have an enhanced ability to metastasize in patients with low plasma SDF-1 levels. In this study, we determined the prognostic significance of activated CXCR4, or phosphorylated CXCR4 (p-CXCR4), and CXCR7, another receptor for SDF-1. Immunohistochemistry was performed on a tissue microarray built using 237 samples from the same cohort of patients for which we measured plasma SDF-1 levels. We found that the prognostic value of p-CXCR4 expression (hazard ratio or HR, 3.95; P ‫؍‬ 0.004) was superior to total CXCR4 expression (HR, 3.20; P ‫؍‬ 0.03). The rate of breast cancer-specific mortality was much higher in patients with both high p-CXCR4 expression and low plasma SDF-1 levels (HR, 5.96; P < 0.001) than either low plasma SDF-1 (HR, 3.59; P ‫؍‬ 0.01) or high p-CXCR4

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Section: Discussionmentioning

confidence: 99%

The Influence of Tumor-Host Interactions in the Stromal Cell-Derived Factor-1/CXCR4 Ligand/Receptor Axis in Determining Metastatic Risk in Breast Cancer

Hassan

Ferrario

Saragovi

et al. 2009

The American Journal of Pathology

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“…AMD3100) already being tested for hematopoietic stem cell mobilisation [28], anti-human CXCR4 or CXCL12 antibodies and modified CXCL12 peptides (e.g. CTCE-9908 or CTCE-0214), have been tested to inhibit this pathway [29][30][31]. Up to now, CXCR4 antagonism is the most relevant and advanced chemokine antagonism envisioned in B-CLL treatment.…”

Section: Cxcl12 (Sdf-1) and Its Receptor Cxcr4mentioning

confidence: 99%

The role of chemokines in B cell chronic lymphocytic leukaemia: pathophysiological aspects and clinical impact

2009

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International audienceChemokines are centrally involved in leukocyte migration, homing and haematopoiesis. Besides these physiological aspects, their role in pathological processes especially with respect to solid tumour and haematological neoplasias is well established. In this context, the focus was set here on disclosing their contribution in B cell chronic lymphocytic leukaemia (B-CLL), which is regarded as the most characteristic low-grade lymphoma. Up to now, it has been demonstrated that several chemokines are involved in migration of B-CLL cells to lymph nodes, secondary lymphoid organs and bone marrow. Moreover, some chemokines are known to have an anti-apoptotic effect and thus contribute to the survival of B-CLL cells. By interfering with both of these aspects, new therapeutic targets for this yet incurable disease may be developed. Furthermore, a correlation can be drawn between the concentration of some chemokines in patients' serum, the expression of their respective receptors on B-CLL cells and well-established predictive clinical parameters. Consequently, further systematic investigation of the chemokine network may lead to the identification of new diagnostic and prognostic markers. This review focuses on the impact of chemokines and their receptors on B-CLL pathophysiology and points out potential implications for both treatment and diagnosis

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“…148 CTCE-9908, a peptide analog of stromal cell-derived factor-1 that acts as a competitive antagonist of CXCR4, has been studied in a Phase I/II clinical trial. It showed some preliminary signs of activity, with five patients having stable disease among the 30 patients who received the drug (including eight patients with breast cancer).…”

mentioning

confidence: 99%

Optimal management of bone metastases in breast cancer patients

Wong

Pavlakis

2011

BCTT

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Bone metastasis in breast cancer is a significant clinical problem. It not only indicates incurable disease with a guarded prognosis, but is also associated with skeletal-related morbidities including bone pain, pathological fractures, spinal cord compression, and hypercalcemia. In recent years, the mechanism of bone metastasis has been further elucidated. Bone metastasis involves a vicious cycle of close interaction between the tumor and the bone microenvironment. In patients with bone metastases, the goal of management is to prevent further skeletal-related events, manage complications, reduce bone pain, and improve quality of life. Bisphosphonates are a proven therapy for the above indications. Recently, a drug of a different class, the RANK ligand antibody, denosumab, has been shown to reduce skeletal-related events more than the bisphosphonate, zoledronic acid. Other strategies of clinical value may include surgery, radiotherapy, radiopharmaceuticals, and, of course, effective systemic therapy. In early breast cancer, bisphosphonates may have an antitumor effect and prevent both bone and non-bone metastases. Whilst two important Phase III trials with conflicting results have led to controversy in this topic, final results from these and other key Phase III trials must still be awaited before a firm conclusion can be drawn about the use of bisphosphonates in this setting. Advances in bone markers, predictive biomarkers, multi-imaging modalities, and the introduction of novel agents have ushered in a new era of proactive management for bone metastases in breast cancer.

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Translating an Antagonist of Chemokine Receptor CXCR4: From Bench to Bedside

Cited by 170 publications

References 55 publications

The Influence of Tumor-Host Interactions in the Stromal Cell-Derived Factor-1/CXCR4 Ligand/Receptor Axis in Determining Metastatic Risk in Breast Cancer

The Influence of Tumor-Host Interactions in the Stromal Cell-Derived Factor-1/CXCR4 Ligand/Receptor Axis in Determining Metastatic Risk in Breast Cancer

The role of chemokines in B cell chronic lymphocytic leukaemia: pathophysiological aspects and clinical impact

Optimal management of bone metastases in breast cancer patients

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