Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland.
Int J Mol Sci. 2023 Feb 25;24(5):4539. doi: 10.3390/ijms24054539.
In recent years, our understanding of the epigenetic mechanisms involved in tumor pathology has improved greatly. DNA and histone modifications, such as methylation, demethylation, acetylation, and deacetylation, can lead to the up-regulation of oncogenic genes, as well as the suppression of tumor suppressor genes. Gene expression can also be modified on a post-transcriptional level by microRNAs that contribute to carcinogenesis. The role of these modifications has been already described in many tumors, e.g., colorectal, breast, and prostate cancers. These mechanisms have also begun to be investigated in less common tumors, such as sarcomas. Chondrosarcoma (CS) is a rare type of tumor that belongs to sarcomas and is the second most common malignant bone tumor after osteosarcoma. Due to unknown pathogenesis and resistance to chemo- and radiotherapies of these tumors, there is a need to develop new potential therapies against CS. In this review, we summarize current knowledge on the influence of epigenetic alterations in the pathogenesis of CS by discussing potential candidates for future therapies. We also emphasize ongoing clinical trials that use drugs targeting epigenetic modifications in CS treatment.
近年来，我们对肿瘤病理学中涉及的表观遗传机制的理解有了很大的提高。DNA 和组蛋白的修饰，如甲基化、去甲基化、乙酰化和去乙酰化，可以导致致癌基因的上调，以及肿瘤抑制基因的抑制。微小 RNA 也可以在转录后水平修饰基因表达，从而促进癌症的发生。这些修饰在许多肿瘤中已经得到了描述，如结直肠癌、乳腺癌和前列腺癌。这些机制也开始在不太常见的肿瘤中进行研究，如肉瘤。软骨肉瘤（CS）是一种罕见的肿瘤，属于肉瘤，是继骨肉瘤之后第二常见的恶性骨肿瘤。由于这些肿瘤的发病机制不明，且对化疗和放疗有耐药性，因此需要开发针对 CS 的新的潜在治疗方法。在这篇综述中，我们通过讨论 CS 发病机制中潜在的治疗靶点，总结了目前关于表观遗传改变影响的知识。我们还强调了正在进行的临床试验，这些试验使用针对 CS 治疗中表观遗传修饰的药物。
