Bruschi Alessandro, Sambri Andrea, Fiore Michele, Bubbico Elisa, Scollo Cristina, Pace Andrea, Zunarelli Renato, Montanari Andrea, Cappelli Alberta, Di Prinzio Lorenzo, De Paolis Massimiliano
Orthopedic and Traumatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Cancer Med. 2025 May;14(9):e70901. doi: 10.1002/cam4.70901.
Bone metastases and pathological fractures significantly impact the prognosis and quality of life in cancer patients. However, clinical and radiological features alone have been shown to fail to predict skeletal related events of a bone metastasis (SREs).
This study focuses on key molecular players including Matrix Metalloproteinases (MMPs), Integrins, Bone Morphogenetic Proteins (BMPs), Parathormone-related Protein (PTHrP).
The RANK/RANKL/Osteoprotegerin (OPG) pathway, and N-terminal peptide (NTx), involved in the metastatic process and bone integrity disruption. Elevated levels of these molecules have been pointed out as potential biomarkers for predicting SREs, but they have been poorly investigated. Moreover, batimastat, marimastat, tanomastat, andecaliximab, and HIV protease targeting MMPs; Volociximab/M200, cilengitide, abituzumab, and FAK inhibitors targeting integrins; LDN193189, DMH1, and ISLR modulators targeting BMPs; and PTH (7-33)-CBD targeting PTHrP have shown promising results antagonizing these molecules, but no effect on preventing and managing metastatic fractures has been assessed yet.
This paper underscores the importance of advanced molecular biology and transcriptomics in identifying novel therapeutic targets. The integration of these biomarkers with clinical and radiological assessments using artificial intelligence tools could revolutionize the diagnostics and treatment strategies for patients with bone metastases.
骨转移和病理性骨折对癌症患者的预后和生活质量有显著影响。然而，仅临床和放射学特征已被证明无法预测骨转移的骨相关事件（SREs）。
本研究聚焦于关键分子参与者，包括基质金属蛋白酶（MMPs）、整合素、骨形态发生蛋白（BMPs）、甲状旁腺激素相关蛋白（PTHrP）。
RANK/RANKL/骨保护素（OPG）途径以及N端肽（NTx）参与转移过程和骨完整性破坏。这些分子水平的升高已被指出是预测SREs的潜在生物标志物，但对它们的研究较少。此外，靶向MMPs的batimastat、marimastat、tanomastat和ecaliximab，以及HIV蛋白酶；靶向整合素的Volociximab/M200、西仑吉肽、abituzumab和FAK抑制剂；靶向BMPs的LDN193189、DMH1和ISLR调节剂；以及靶向PTHrP的PTH（7-33）-CBD在拮抗这些分子方面已显示出有前景的结果，但尚未评估其对预防和处理转移性骨折的效果。
本文强调了先进分子生物学和转录组学在识别新型治疗靶点方面的重要性。使用人工智能工具将这些生物标志物与临床和放射学评估相结合，可能会彻底改变骨转移患者的诊断和治疗策略。
