TREATMENT STRATEGIES WITH MOLECULAR MARKERS AND TARGETED THERAPEUTICS IN METASTATIC TUMORS OF THE SPINE

Spinal metastases occur in approximately 15% of patients with solid tumors and up to 30% in autopsy series, with breast, prostate, thyroid, lung, and kidney cancers being the primary sources. These lesions cause severe complications such as pathological fractures, spinal cord compression, and hypercalce-mia, resulting in a poor 5-year overall survival rate of around 24%. Traditional treatments like surgical decompression, stabilization, and radiotherapy offer symptom relief but have limited curative poten-tial, especially for multifocal disease. Systemic chemotherapy poorly penetrates the bone microenvi-ronment and carries significant toxicity, motivating the development of targeted therapies. RANKL plays a central role in osteoclast activation and metastatic progression; its inhibition with agents like denosumab improves outcomes. Advances in molecular oncology have identified key biomarkers and pathways driving bone metastasis, including HER2 amplification and PIK3CA mutations in breast cancer, PTEN loss and TMPRSS2-ERG fusion in prostate cancer, and EGFR mutations and ALK/ ROS1 rearrangements in lung cancer. These molecular features guide personalized systemic therapies and surgical planning. Immunotherapies targeting PD-1/PD-L1 show efficacy, especially in tumors with high PD-L1 expression and tumor mutational burden. However, bone metastases may reduce their effectiveness because the metastatic bone microenvironment is immunosuppressive, involving regulatory T cells and tumor-associated macrophages, which facilitate tumor growth. Recent advances in molecularly targeted combination therapies, artificial-intelligence–driven decision-support systems, and gene-editing technologies collectively herald a paradigm shift that could fundamentally reshape the diagnostic and therapeutic algorithms for spinal metastases in the coming years. In contempo-rary management of spinal metastases, comprehensive molecular profiling has, as in other metastatic settings, become virtually the gold standard. Nevertheless, patient-specific molecular data are still reviewed as fragmented reports during Molecular Tumor Board meetings, and no readily available solution yet consolidates these findings into a single, continuously updated, real-time “molecular data card” capable of guiding treatment sequencing through automated alerts. Developing such a platform would enable truly dynamic, individualized ordering of surgery, radiotherapy, and systemic therapy.