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恶性葡萄膜黑色素瘤的表观遗传变化及其治疗靶向的可能性

EPIGENETIC CHANGES IN MALIGNANT UVEAL MELANOMA AND POSSIBILITIES OF THEIR THERAPEUTIC TARGETING.

作者信息

Smolková B, Demková L

出版信息

Cesk Slov Oftalmol. 2020 Spring;76(2):55-60. doi: 10.31348/2020/12.

Abstract

Uveal melanoma (UM) is a deadly cancer that leads to metastatic disease in more than 50 % of the patients. Despite the improvement in the treatment of primary disease, there is still no effective therapy to prevent the development of metastases. Therefore, the disease requires intensive research to identify new treatment strategies. In preclinical UM models, epigenetic drugs have been shown to increase the sensitivity of resistant tumour cells to treatment. The successful use of histone deacetylase inhibitors, which induced cell cycle arrest, reprogramming consistent with melanocyte differentiation and inhibition of tumour growth in preclinical models, demonstrates the role of epigenetic regulation in UM metastasis. Identification of epigenetic changes associated with UM development an progression could contribute to the discovery of more effective drugs that, in combination with traditional approaches, may yield better therapeutic results for high-risk patients.

摘要

葡萄膜黑色素瘤(UM)是一种致命的癌症,超过50%的患者会发展为转移性疾病。尽管原发性疾病的治疗有所改善,但仍没有有效的疗法来预防转移的发生。因此,该疾病需要深入研究以确定新的治疗策略。在临床前UM模型中,表观遗传药物已被证明可提高耐药肿瘤细胞对治疗的敏感性。组蛋白去乙酰化酶抑制剂在临床前模型中诱导细胞周期停滞、与黑素细胞分化一致的重编程以及抑制肿瘤生长,其成功应用证明了表观遗传调控在UM转移中的作用。识别与UM发生和进展相关的表观遗传变化可能有助于发现更有效的药物,这些药物与传统方法联合使用,可能会为高危患者带来更好的治疗效果。

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