EGFR and HER3 signaling blockade in invasive mucinous lung adenocarcinoma harboring an NRG1 fusion
EGFR and HER3 signaling blockade in invasive mucinous lung adenocarcinoma harboring an NRG1 fusion
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DOI：
10.1016/j.lungcan.2018.07.026
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发表时间：
2018-10-01
期刊：
影响因子：
5.3
通讯作者：
James, I
中科院分区：
文献类型：
--
作者：
Kim, Hye Sook;Han, Ji-Youn;James, I
NRG 1的重排已经在侵袭性肺粘液腺癌（IMA）中被鉴定，以前被称为粘液性细支气管肺泡癌。NRG 1配体通过诱导HER 2-HER 3异源二聚体发出信号，从而导致PI 3 K-AKT途径活化。因此，靶向HER 2、HER 3及其下游通路可能是IMA与NRG 1融合的假设驱动策略。在此，我们报告了两名患者在临床试验（NCT 01482377）期间受益于Lumretuzumab（一种单克隆抗HER 3抗体）联合厄洛替尼。至少16周的无进展生存期没有任何不可接受的毒性。
Rearrangements of NRG1 have been identified in invasive mucinous adenocarcinoma of the lung (IMA), formerly referred to as mucinous bronchioloalveolar carcinoma. NRG1 ligand signals through induction of HER2-HER3 heterodimers, thus leading to PI3K-AKT pathway activation. Therefore, targeting HER2, HER3 and the downstream pathway may be a hypothesis-driven strategy for IMA with NRG1 fusion. Herein we reported two patients who benefited from lumretuzumab, a monoclonal anti-HER3 antibody, in combination of erlotinib during a clinical trial (NCT01482377). At least sixteen weeks of progression-free survival were achieved without any unacceptable toxicity.