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[BRAFV600 突变转移性黑色素瘤中致癌副作用及对 BRAF 抑制剂耐药的细胞与分子机制:知识现状]

[Cellular and molecular mechanisms of carcinogenic side effects and resistance to BRAF inhibitors in metastatic melanoma with BRAFV600 mutation: state of the knowledge].

作者信息

Capovilla Mathieu

机构信息

Service de pathologie, centre François-Baclesse, 3, avenue Général-Harris, BP 5026, 14076 Caen cedex 05, France.

出版信息

Ann Pathol. 2013 Dec;33(6):375-85. doi: 10.1016/j.annpat.2013.09.003. Epub 2013 Oct 31.

Abstract

Cutaneous melanoma is a malignant tumor with a high metastatic potential. If an early treatment is associated with a favorable outcome, the prognosis of metastatic melanoma remains poor. Advances in molecular characterization of cancers, notably the discovery of BRAF gene mutations in metastatic melanoma, allowed to the recent development of targeted therapies against mutated BRAF protein. Despite high tumor response rates observed in clinical trials, these new drugs are associated with frequent secondary tumor resistance occurrence and paradoxical carcinogenic side effects. The cellular and molecular mechanisms of these carcinogenic side effects and secondary resistance are not yet fully elucidated and are actually intensely studied. This review of the literature focus on the mechanisms of these carcinogenic side effects and on the tumor resistance associated with anti-BRAF targeted therapies.

摘要

皮肤黑色素瘤是一种具有高转移潜能的恶性肿瘤。如果早期治疗能带来良好的预后,那么转移性黑色素瘤的预后仍然很差。癌症分子特征研究的进展,特别是在转移性黑色素瘤中发现BRAF基因突变,促使了针对突变BRAF蛋白的靶向治疗的近期发展。尽管在临床试验中观察到较高的肿瘤反应率,但这些新药常伴有继发性肿瘤耐药的发生以及矛盾的致癌副作用。这些致癌副作用和继发性耐药的细胞和分子机制尚未完全阐明,目前正在深入研究。这篇文献综述聚焦于这些致癌副作用的机制以及与抗BRAF靶向治疗相关的肿瘤耐药性。

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