Title:SHP2 Inhibition Benefits Epidermal Growth Factor Receptor-mutated Non-Small Cell Lung Cancer Therapy
Volume: 21
Issue: 11
Author(s): Leiming Xia, Lu Wen and Siying Wang*
Affiliation:
- Basic College of Medicine, Anhui Medical University, Hefei,China
Keywords:
EGFR-TKIs, mutation, SHP2, drug resistence, inhibition, NSCLC.
Abstract: 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
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of SHP2 inhibitor combined with EGFR-TKIs.
