Chordoma represents a central nervous system tumor with an incidence of 8.4 per 10 million individuals in the U.S. Current treatment options include surgical resection and radiotherapy. Despite recent studies demonstrating significant improvement in molecular understanding of disease, treatment options remain limited. To evaluate a database of high-throughput drug screening in conjunction with a systematic literature review of potential novel target sites. A systematic review using terms "chordoma" AND "targeted therapy" OR "clinical trial" yielded 4560 articles, which were screened, and a total of 88 were included in the final analysis. Evaluation of the Chordoma Foundation high-throughput drug screening database was cross-referenced with published literature. Targeted therapies mostly involved receptor tyrosine kinase inhibitors. Cyclin-dependent kinase (CDK) inhibitors suppressed chordoma cell proliferation and brachyury expression in vitro and xenograft models. Epigenetic modulators showed therapeutic promise by altering chromatin states associated with brachyury overexpression. Genomic analyses showed recurrent alterations in TBXT, CDKN2A/B, PTEN, and chromatin remodeling genes such as SMARCB1 and PBRM1. Immunotherapeutic approaches had efficacy in preclinical models through PD-L1 blockade, NK, and CAR-T cell strategies. Vaccine-based therapies showed limited clinical benefit. RNA-based therapies represent emerging strategies that need more studies. Biomarker-guided repurposing of therapies approved in other tumors remains the fastest path to redefining the treatment model, but chordoma rarity and low mutation burden limit the impact of genomics in target discovery. This analysis indicates several potential candidate drugs that may be rapidly deployable in a clinical trial setting.

Background: Intracranial atherosclerotic disease (ICAD) remains a major global cause of ischemic stroke—particularly in Asian, Black, and Hispanic populations—and is characterized by high recurrence rates despite advances in intensive medical management. Objectives: This review synthesizes current evidence on surgical and endovascular approaches for ICAD, including extracranial–intracranial bypass, encephaloduroarteriosynangiosis, angioplasty, and hybrid revascularization strategies. Methods: We performed a structured narrative literature search of PubMed and Scopus. Searches were conducted up to 1 October 2025 using combinations of subject headings and keywords, including “intracranial atherosclerotic disease”, “ICAD”, “intracranial stenosis”, “bypass”, “encephaloduroarteriosynangiosis”, “angioplasty”, “stenting”, “revascularization”, and “stroke”. We also scanned reference lists of key articles and relevant reviews. Non-English language articles were excluded. Results: While randomized trials such as SAMMPRIS, VISSIT, and CASSISS reaffirm intensive medical management as first-line therapy, emerging data suggest that surgical revascularization may benefit select patients with hemodynamic compromise refractory to medical therapy. Recent studies incorporating physiologic imaging—such as PET, SPECT, and perfusion MRI—have refined patient selection, reducing perioperative risk and improving long-term outcomes. Innovations in indirect revascularization, hybrid procedures, and intraoperative imaging continue to expand therapeutic possibilities. However, evidence remains heterogeneous, underscoring the need for well-powered randomized trials integrating modern surgical techniques, objective hemodynamic endpoints, and AI-enhanced imaging analytics. Conclusions: While intensive medical management remains the first-line standard of care, select patients with refractory, hemodynamically significant ICAD may benefit from direct, indirect, or hybrid surgical revascularization. Future directions emphasize personalized, physiology-based management frameworks that combine medical, surgical, and technological advances to optimize stroke prevention and long-term vascular outcomes in ICAD.