For many spine surgeons, patients with metastatic cancer are often present in an emergent situation with rapidly progressive neurological dysfunction. Since the Patchell trial, scoring systems such as NOMS and SINS have emerged to guide the extent of surgical excision and fusion in the context of chemotherapy and radiation therapy. Yet, while multidisciplinary decision-making is the gold standard of cancer care, in the middle of the night, when a patient needs spinal surgery, the wealth of chemotherapy data, clinical trials, and other medical advances can feel overwhelming. The goal of this review is to provide an overview of the relevant molecular biomarkers and therapies driving patient survival in lung, breast, prostate, and renal cell cancer. We highlight the molecular differences between primary tumors (i.e., the patient’s original lung cancer) and the subsequent spinal metastasis. This distinction is crucial, as there are limited data investigating how metastases respond to their primary tumor’s targeted molecular therapies. Integrating information from primary and metastatic markers allows for a more comprehensive and personalized approach to cancer treatment.

Background: Schwann cells (SCs) and their plasticity contribute to the peripheral nervous system’s capacity for nerve regeneration after injury. The Egr2/Krox20 promoter antisense RNA (Egr2-AS) recruits chromatin remodeling complexes to inhibit Egr2 transcription following peripheral nerve injury. Methods: RNA-seq and ATAC-seq were performed on control cells, Lenti-GFP-transduced cells, and cells overexpressing Egr2-AS (Lenti-AS). Egr2 AS-RNA was cloned into the pLVX-DsRed-Express2-N1 lentiviral expression vector (Clontech, Mountain View, CA, USA), and the levels of AS-RNA expression were determined. Ezh2 and Wdr5 were immunoprecipitated from rat SCs and RT-qPCR was performed against AS-Egr2 RNA. ChIP followed by DNA purification columns was used to perform qPCR for relevant promoters. Hi-C, HiC-DC+, R, Bioconductor, and TOBIAS were used for significant and differential loop analysis, identifications of COREs and CORE-promotor loops, comparisons of TF activity at promoter sites, and identification of site-specific TF footprints. OnTAD was used to detect TADs, and Juicer was used to identify A/B compartments. Results: Here we show that a Neuregulin-ErbB2/3 signaling axis mediates binding of the Egr2-AS to YY1^Ser184 and regulates its expression. Egr2-AS modulates the chromatin accessibility of Schwann cells and interacts with two distinct histone modification complexes. It binds to EZH2 and WDR5 and enables targeting of H3K27me3 and H3K4me3 to promoters of Egr2 and C-JUN, respectively. Expression of the Egr2-AS results in reorganization of the global chromatin landscape and quantitative changes in the loop formation and contact frequency at domain boundaries exhibiting enrichment for AP-1 genes. In addition, the Egr2-AS induces changes in the hierarchical TADs and increases transcription factor binding scores on an inter-TAD loop between a super-enhancer regulatory hub and the promoter of mTOR. Conclusions: Our results show that Neuregulin-ErbB2/3-YY1 regulates the expression of Egr2-AS, which mediates remodeling of the chromatin landscape in Schwann cells.

Chordomas are rare, highly morbid tumors arising from notochordal progenitor cells along the spinal axis, associated with severe neurological complications and high recurrence rates. Their resistance to conventional therapies and limited options beyond surgical resection and high-dose radiation underscore the urgent need for novel therapeutic targets. Publicly available preliminary RNA sequencing data from the Chordoma Foundation identified chitinase-3-like 1 (CHI3L1), a secreted glycoprotein implicated in immune checkpoint regulation and epithelial–mesenchymal transition (EMT), as a promising candidate for chordoma immunotherapy. Yet, the comprehensive function of CHI3L1 in chordoma immune response remains unclear. To evaluate its presence in chordoma, we employed RNA-based analyses alongside enzyme-linked immunosorbent assays (ELISA) on commercially available chordoma cell lines (JHC7, U-CH12, U-CH1, U-CH1-N) and human chordoma tumor specimens. Our results demonstrate elevated CHI3L1 expression in chordoma cells relative to notochordal precursors, with comparative analyses revealing higher CHI3L1 expression in the primary tumor relative to recurrent samples. These findings suggest the potential role of CHI3L1 in chordoma tumorigenesis, emphasizing its relevance as a biomarker and therapeutic target for primary tumors. Future studies are necessary to elucidate the mechanistic role of CHI3L1 in chordoma immune evasion and to explore targeted interventions that may improve patient outcomes in this aggressive cancer.

Advances in surgical techniques and equipment, oncological therapies, and genetic analyses have resulted in strides forward for the management of spine tumor patients. 1,2 The Research Topic "Translational Research in Surgical Applications and Spinal Tumors" provides an overview of diverse topics related to improving patient care and outcomes in spinal surgery and oncology. This editorial presents the key findings and takeaways from each article in this Research Topic, which aims to compile recent translational work on spinal tumors and their management.Quality of life and its selected determinants in the group of patients with surgically treated spinal tumorsThe first article explores spine tumor patients' quality of life before and after spine stabilization and spinal cord decompression. This single-center prospective study found that patients' physical and psychological symptoms were significantly reduced after surgery and level of activity, disease acceptance, and perceived quality of life were significantly increased. This piece highlights the impacts of spine surgery on not only the physical but also emotional and psychological health of spinal oncology patients, which has important implications for patient recovery and satisfaction.An unusual presentation of ossified spinal meningioma: case report and literature reviewThe second article presents a rare case of ossified spinal meningioma, one of only 43 that have been cited until 2022. This case details the successful total resection of an ossified meningioma and highlights potential strategies for and obstacles to surgical resection as well as diagnostic mechanisms, all of which lead to improved management of these rare tumors. Clinical exploration of the international society of limb salvage classification of end-prosthetic failure using Henderson in the application of 3D-printed pelvic tumor prosthesesThe third article compiles the results of a single-institution retrospective analysis of patients with 3D-printed pelvic tumor prostheses after tumor resection. The authors utilized the Henderson concepts for evaluating the efficacy of 3D-printed prosthetics and found that patients overall had satisfactory structural stability and effective function postoperatively. This paper demonstrates the potential for improved outcomes in pelvic tumor resection with the application of prosthetic devices designed based on the Henderson subtypes, which allows for both improved surgical construct planning and patient quality of life and function.Association of quantitative radiomic shape features with functional outcome after surgery for primary sporadic dorsal spinal meningiomasThe fourth article details a retrospective analysis of shape-based radiomic features of dorsal spinal meningiomas. The study found that increasing tumor sphericity was associated with improved neurological function following resection. These results suggest that preoperative shape-based analyses of spinal meningiomas could have both surgical planning and prognostic implications for patients, which could allow for better selection of surgical candidates and more accurate predictions of postoperative neurological status.Comparison of clinical efficacy of 3D-printed artificial vertebral body and conventional titanium mesh cage in spinal reconstruction after total en bloc spondylectomy for spinal tumors: a systematic review and meta analysisThe fifth article presents a meta-analysis comparing the efficacy of 3D-printed artificial vertebral bodies (AVBs) to conventional titanium mesh cages (TMCs) in spine tumor patients after total en bloc spondylectomy. The analysis revealed that surgeries utilizing 3D-printed AVBs had significantly improved intraoperative and postoperative outcomes than those performed with TMCs. These results suggest that the material used for reconstruction should be carefully considered by spine surgeons, as it could have a significant impact on postoperative function and patient satisfaction.The sixth article evaluates the survival outcomes in elderly patients with chordoma following gross total resection (GTR). This study found that although spine surgeons are often hesitant to perform aggressive surgical resections on elderly patients, patients 40-59 and 80-99 had a lower risk of mortality after GTR compared to patients who were managed nonoperatively. These findings support offering GTR to patients regardless of age, which can improve patient outcomes.The seventh article presents the current understanding of various humanized mouse models that are used in immunotherapy research for chordoma. Based on the literature, the authors suggest that humanized immunocompetent mice are better suited for studying the tumor microenvironment and subsequent immune involvement while immunocompromised mice are more useful for studying tumor growth and treatments independent of the immune system. This overview of various mouse models can be a helpful resource for researchers studying chordoma.The final article details the results of eight case studies and one clinical trial on the use of immunotherapy in treatment-refractory chordoma. The authors found that most patients in the case studies experienced temporary tumor regression and symptom improvement before the disease progressed, and the clinical trial observed little difference between the treatment and control arms such that it was discontinued. These results underscore the importance of continuing research into immunotherapies for chordoma as well as the need for increased understanding of the tumor microenvironment in order to design future studies.The articles compiled within this Research Topic illustrate a wide variety of advances, obstacles, and future directions for spinal surgery and oncology. While the exploration of genetic marker congruence between primary and metastatic spinal tumors remains an important area of study, this collection lacks an article dedicated to this complex issue, and the...

Chordomas are primary tumors of the skull base and vertebral column typically derived from the notochord. Treatment options consist of surgical resection, radiotherapy, and chemotherapy. This study reviews clinical trials focused on radiotherapy techniques, such as photon therapy and carbon ion radiotherapy, as well as the concomitant use of radia-tion sensitizers. We completed a literature review on all published clinical trials on the usage of photon, proton, and carbon ion radiotherapy (CIRT) for chordoma in adults and all published literature on radiation sensitizers used for treatment in chordoma from 2000 to 2025. We reviewed all nine current clinical trials on radiotherapy for chordoma in adults. All clinical trials were able to achieve an overall survival rate above 50% at 3-year follow-up. Seven publications were found on the use of radiation sensitizers for chordomas, both in vitro and in vivo. The completed clinical trials evaluate the effectiveness of proton, photon, and CIRT for treatment of the skull base, spine, and sacral chordoma. Current trials continue these efforts and compare the different radiotherapies and determine appropriate doses. Research on radiation sensitizers for chordomas shows various therapies, ranging from hyperthermia to pharmaceutical options, that require further study.

Chordomas are rare, highly morbid tumors arising from notochordal progenitor cells along the spinal axis, associated with severe neurological complications and high recurrence rates. Their resistance to conventional therapies and limited options beyond surgical resection and high-dose radiation underscore the urgent need for novel therapeutic targets. Publicly available preliminary RNA sequencing data from the Chordoma Foundation identified chitinase-3-like 1 (CHI3L1), a secreted glycoprotein implicated in immune checkpoint regulation and epithelial-mesenchymal transition (EMT), as a promising candidate for chordoma immunotherapy. Yet, the comprehensive function of CHI3L1 in chordoma immune response remains unclear. To evaluate its presence in chordoma, we employed RNA-based analyses alongside enzyme-linked immunosorbent assays (ELISA) on commercially available chordoma cell lines (JHC7, U-CH12, U-CH1, U-CH1-N) and human chordoma tumor specimens. Our results demonstrate elevated CHI3L1 expression in chordoma cells relative to notochordal precursors, with comparative analyses revealing higher CHI3L1 expression in the primary tumor relative to recurrent samples. These findings suggest the potential role of CHI3L1 in chordoma tumorigenesis, emphasizing its relevance as a biomarker and therapeutic target for primary tumors. Future studies are necessary to elucidate the mechanistic role of CHI3L1 in chordoma immune evasion and to explore targeted interventions that may improve patient outcomes in this aggressive cancer.