Chantre-Justino Mariana, Meohas Walter
Research Division, National Institute of Traumatology and Orthopaedics, Rio de Janeiro 20940-070, Brazil.
Specialized Care Center for Orthopedic Oncology, National Institute of Traumatology and Orthopaedics, Rio de Janeiro 20940-070, Brazil.
Explor Target Antitumor Ther. 2025 May 26;6:1002319. doi: 10.37349/etat.2025.1002319. eCollection 2025.
Musculoskeletal sarcomas represent heterogeneous and rare malignant bone and soft tissue tumors, affecting children and adults. Patients exhibiting poor clinical outcomes are often described, being associated with non-response to chemotherapy, amputation needs, or metastatic disease. Potential biomarkers contributing to diagnosis, prognosis, and treatment response could improve this scenario. Despite this, little is known about the genomic aspects of musculoskeletal sarcomas. DNA methylation is the most studied epigenetic mechanism, where changes in methylation profiling are characteristic hallmarks of cancer. Cancer-related methylome profiling has been investigated both in tumor biopsies (genomic DNA) and liquid biopsies (cell-free DNA). Epigenetic therapies by using DNA-demethylating drugs are promising strategies for cancer treatment. This review will discuss translational studies describing how DNA methylation landscape of musculoskeletal sarcomas can be a powerful molecular tool to improve diagnostic accuracy, predict prognosis, and treatment response. Additionally, this review will describe the promising role of epigenetics-targeted drugs as well as the ongoing clinical trials for sarcomas, highlighting the challenges and future directions.
肌肉骨骼肉瘤是一类异质性的罕见恶性骨和软组织肿瘤，可发生于儿童和成人。常描述有临床预后较差的患者，这与化疗无反应、需要截肢或转移性疾病有关。有助于诊断、预后和治疗反应的潜在生物标志物可能会改善这种情况。尽管如此，人们对肌肉骨骼肉瘤的基因组方面知之甚少。DNA甲基化是研究最多的表观遗传机制，甲基化谱的变化是癌症的特征性标志。已在肿瘤活检（基因组DNA）和液体活检（游离DNA）中研究了与癌症相关的甲基化组谱。使用DNA去甲基化药物的表观遗传疗法是很有前景的癌症治疗策略。本综述将讨论转化研究，描述肌肉骨骼肉瘤的DNA甲基化格局如何成为提高诊断准确性、预测预后和治疗反应的有力分子工具。此外，本综述将描述表观遗传学靶向药物的前景作用以及肉瘤正在进行的临床试验，突出挑战和未来方向。
