Inside a Metastatic Fracture: Molecular Bases and New Potential Therapeutic Targets

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.