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Resistance mechanisms to targeted therapy in BRAF-mutant melanoma - A mini review.
Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 3 ) Pub Date : 2020-09-18 , DOI: 10.1016/j.bbagen.2020.129736
Lokeswari P Tangella 1 , Michael E Clark 1 , Elin S Gray 1
Affiliation  

Background

The introduction of targeted therapies for the treatment of BRAF-mutant melanomas have improved survival rates in a significant proportion of patients. Nonetheless, the emergence of resistance to treatment remains inevitable in most patients.

Scope of review

Here, we review known and emerging molecular mechanisms that underlay the development of resistance to MAPK inhibition in melanoma cells and the potential strategies to overcome these mechanisms.

Major conclusions

Multiple genetic and non-genetic mechanisms contribute to treatment failure, commonly leading to the reactivation of the MAPK pathway. A variety of resistance mechanisms are enabled by the underlying heterogeneity and plasticity of melanoma cells. Moreover, it has become apparent that resistance to targeted therapy is underpinned by early functional adaptations involving the rewiring of cell states and metabolic pathways.

General significance

The evidence presented suggest that the use of a combinatorial treatment approach would delay the emergence of resistance and improve patient outcomes.



中文翻译:

对BRAF突变型黑色素瘤靶向治疗的耐药机制-小型回顾。

背景

引入靶向治疗BRAF突变型黑色素瘤的疗法在相当大比例的患者中提高了生存率。尽管如此,在大多数患者中仍不可避免出现抗药性。

审查范围

在这里,我们审查了已知和新兴的分子机制,这些机制奠定了黑色素瘤细胞对MAPK抑制的抗性发展以及克服这些机制的潜在策略。

主要结论

多种遗传和非遗传机制导致治疗失败,通常导致MAPK通路重新激活。黑色素瘤细胞潜在的异质性和可塑性使多种耐药机制成为可能。此外,很明显,针对靶向治疗的抗性由涉及细胞状态和代谢途径重新接线的早期功能适应所支撑。

一般意义

提出的证据表明,联合治疗方法的使用将延迟耐药性的出现并改善患者预后。

更新日期:2020-09-22
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