The role of MET in chemotherapy resistance.

The role of MET in chemotherapy resistance.
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DOI:
10.1038/s41388-020-01577-5
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发表时间:
2021-03
期刊:
影响因子:
8
通讯作者:
Kermorgant S
Kermorgant S
中科院分区:
医学1区
文献类型:
--
作者:
Wood GE;Hockings H;Hilton DM;Kermorgant S

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化疗仍然是大多数实体和血液恶性肿瘤的主要治疗方法。对细胞毒性化疗的抗性是一个主要的临床问题,并且正在进行大量的研究以克服这种抗性的潜在方法。一个主要的靶点,受体酪氨酸激酶MET,随着多项临床试验的进行,引起了越来越多的兴趣。MET的过表达经常在一系列不同的癌症中观察到,并且与不良预后相关。研究表明,MET促进对靶向治疗的耐药性,包括靶向EGFR、BRAF和MEK的治疗。最近,一些报告表明,MET也有助于细胞毒性化疗耐药性。在这里,我们回顾了MET在化疗耐药性中的作用的临床前证据,这种耐药性介导的机制以及MET抑制剂治疗化疗耐药疾病患者的翻译相关性。
Chemotherapy remains the mainstay of treatment in the majority of solid and haematological malignancies. Resistance to cytotoxic chemotherapy is a major clinical problem and substantial research is ongoing into potential methods of overcoming this resistance. One major target, the receptor tyrosine kinase MET, has generated increasing interest with multiple clinical trials in progress. Overexpression of MET is frequently observed in a range of different cancers and is associated with poor prognosis. Studies have shown that MET promotes resistance to targeted therapies, including those targeting EGFR, BRAF and MEK. More recently, several reports suggest that MET also contributes to cytotoxic chemotherapy resistance. Here we review the preclinical evidence of MET’s role in chemotherapy resistance, the mechanisms by which this resistance is mediated and the translational relevance of MET inhibitor therapy for patients with chemotherapy resistant disease.
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