EGFR-TKIs are confronted with big challenge of everlasting activated EGFR mutations which lack effective binding sites; this barrier is the dark side that largely limits the outcome of NSCLC patients in the clinic. Combination strategies show impressive anti-tumor efficacy that compared with EGFR-TKI mono-treatment, especially targeting both stem cells and non-stem cells. SHP2 (Src homology 2-containing phosphotyrosine phosphatase 2) plays an important role in regulating various malignant biology through hyper-activating intracellular pathways due to either overexpression or catalytical mutation. Some pathways, in which SHP2 was involved, were overlapped with EGFR downstream, and others were not subject to EGFR. Interestingly, SHP2 suppression was reported to destroy the stemness of cancer. Therefore, we hypothesize that SHP2 inhibitor might be a promising drug that could synergistically enhance or sensitize the anti-tumor efficacy of EGFR-TKIs in EGFR mutated NSCLC patients. Here, we summarized the mechanisms of SHP2 in regulating EGFR mutated NSCLC patients, and attempted to reveal the potential synergistic file://localhost/C/:Program%20Files%20(x86):Youdao:Dict:7.5.2.0:resultui:dict:%3Fkeyword=effects of SHP2 inhibitor combined with EGFR-TKIs.

EGFR-TKI面临着EGFR突变永久激活、缺乏有效结合位点的巨大挑战；这一障碍是很大程度上限制了临床上非小细胞肺癌患者预后的阴暗面。与 EGFR-TKI 单一治疗相比，联合策略显示出令人印象深刻的抗肿瘤功效，尤其是针对干细胞和非干细胞。SHP2（含 Src 同源 2 的磷酸酪氨酸磷酸酶 2）通过过度表达或催化突变导致的细胞内通路过度激活，在调节各种恶性生物学中发挥重要作用。SHP2参与的一些通路与下游的EGFR重叠，而另一些则不受EGFR的影响。有趣的是，据报道抑制 SHP2 会破坏癌症的干性。所以，我们假设 SHP2 抑制剂可能是一种有前景的药物，可以协同增强或敏感化 EGFR-TKI 在 EGFR 突变的 NSCLC 患者中的抗肿瘤功效。在这里，我们总结了 SHP2 在调节 EGFR 突变 NSCLC 患者中的机制，并试图揭示潜在的协同作用 file://localhost/C/:Program%20Files%20(x86):Youdao:Dict:7.5.2.0:resultui： dict:%3Fkeyword=SHP2 抑制剂联合 EGFR-TKI 的效果。