Translational Windows in Chordoma: A Target Appraisal

Abstract

Chordomas are rare tumors that are notoriously refractory to chemotherapy and radiotherapy when radical surgical resection is not achieved or upon recurrence after maximally aggressive treatment. The study of chordomas has been complicated by small patient cohorts and few available model systems due to the rarity of these tumors. Emerging next-generation sequencing technologies have broadened understanding of this disease by implicating novel pathways for possible targeted therapy. Mutations in cell-cycle regulation and chromatin remodeling genes have been identified in chordomas, but their significance remains unknown. Investigation of the immune microenvironment of these tumors suggests that checkpoint protein expression may influence prognosis, and adjuvant immunotherapy may improve patient outcome. Finally, growing evidence supports aberrant growth factor signaling as potential pathogenic mechanisms in chordoma. In this review, we characterize the impact on treatment opportunities offered by the genomic and immunologic landscape of this tumor.

Clinical Outcomes Following Dose-Escalated Proton Therapy for Skull-Base Chordoma

“…Within the present series, two thirds of patients (20 of 30; 67%%) with locally recurrent disease after treatment either did not attempt salvage (8 of 30; 27%) or were unsuccessful (12 of 30; 40%) without further disease progression to date. It is clear that more innovative options are still needed for this population [ 20 , 21 ].…”

“…Although multimodality therapy incorporating upfront chemotherapy, radiotherapy, and surgery for poorly differentiated tumors may improve oncologic disease control, that issue was not assessed by the present series [ 32 ]. Data analyzing recurrent and metastatic disease are beginning to emerge, and, given the poor prognosis with tumor recurrence, future research should help determine which agents are the most efficacious for the development of novel agents [ 20 , 21 ].…”

Challenges in Diagnosing Chordoma (Skull Base Tumors)

“…Chromosomal changes are found in a few de novo chordomas having poorer prognosis and most common genomic alterations are observed in chromosome numbers 1p, 3, 4, 9, 10, 13, and 14 [11]. It was found that chromosomal gain is less common than chromosomal deletion.…”

“…Chordomas are rare tumors that are notoriously refractory to chemotherapy and radiotherapy and the problems of handling aggressive and refractory chordoma have motivated the study of the biological foundations of this disease [11]. Molecular targeted therapy is an alternative way for the treatment of advanced chordoma [11].…”

“…Chordomas are rare tumors that are notoriously refractory to chemotherapy and radiotherapy and the problems of handling aggressive and refractory chordoma have motivated the study of the biological foundations of this disease [11]. Molecular targeted therapy is an alternative way for the treatment of advanced chordoma [11]. The choice of molecular targeted inhibitors for patients with advanced or relapsed chordoma ought to be based on gene mutation screening and immunohistochemistry.…”