RANKL: A promising circulating marker for bone metastasis response

Ibrahim,Toni; Ricci,Marianna; Scarpi,Emanuela; Bongiovanni,Alberto; Ricci,Rossana; Riva,Nada; Liverani,Chiara; De Vita,Alessandro; La Manna,Federico; Oboldi,Devil; Serra,Patrizia; Foca,Flavia; Cecconetto,Lorenzo; Amadori,Dino; MercatalI,Laura

doi:10.3892/ol.2016.4977

RANKL: A promising circulating marker for bone metastasis response

Authors:
- Toni Ibrahim
- Marianna Ricci
- Emanuela Scarpi
- Alberto Bongiovanni
- Rossana Ricci
- Nada Riva
- Chiara Liverani
- Alessandro De Vita
- Federico La Manna
- Devil Oboldi
- Patrizia Serra
- Flavia Foca
- Lorenzo Cecconetto
- Dino Amadori
- Laura MercatalI
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Affiliations: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I‑47014 Meldola, Italy, Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I‑47014 Meldola, Italy, Radiology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I‑47014 Meldola, Italy, Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I‑47014 Meldola, Italy
Published online on: August 8, 2016 https://doi.org/10.3892/ol.2016.4977
Pages: 2970-2975

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Abstract

Bone metastases are a frequent event in patients with solid tumors. Although great advances have been made in the treatment of these patients, the identification of novel, accurate indicators of bone response would greatly facilitate the clinical management of the disease. The receptor activator of nuclear factor‑κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) signaling pathway is significantly involved in bone metastasis formation. The main aim of the present study was to evaluate the role of circulating RANK, RANKL and OPG levels in predicting bone response. Marker accuracy was also compared with that of the conventional tumor marker N‑terminal telopeptide of type I collagen (NTX). A prospective study was performed on 49 patients with bone metastases from breast, lung and prostate cancer, who were undergoing treatment with zoledronic acid. Patients were monitored for 1 year with blood tests, clinical evaluation and instrumental exams according to the response evaluation criteria of the University of Texas M. D. Anderson Cancer Center (Houston, TX, USA) and the Positron Emission Tomography Response Criteria in Solid Tumors. Circulating RANK/RANKL/OPG transcripts and NTX levels were evaluated by reverse transcription-quantitative polymerase chain reaction and immune enzymatic assay, respectively. The baseline RANKL levels differed significantly between responders and non‑responders, whereas no differences in NTX levels were observed between the two groups. Receiver operating characteristic curve evaluation for all markers revealed that RANKL was the most accurate marker, with an area under the curve of 0.74 (95% confidence interval, 0.54‑0.93). In addition, RANKL, which is the target of the novel monoclonal antibody denosumab, was the most accurate predictor of bone response in the present series of patients with bone metastases. Thus, the use of RANKL as a marker could potentially improve clinical practice, as current bone response evaluation is still somewhat problematic.

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