ArticleAmerican journal of cancer research2022
Targeting SHP2 sensitizes differentiated thyroid carcinoma to the MEK inhibitor.
Article in American journal of cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 7 citations in OpenAlex.
- Inhibition of SHP2 enhances the effects of selective receptor tyrosine kinase inhibitors in untreated preclinical models of RET-mutated thyroid cancer.Investigational new drugs · 2026Article
- SHP2 inhibition and adjuvant therapy synergistically target KIT-mutant GISTs via ERK1/2-regulated GSK3β/cyclin D1 pathway.Clinical and translational medicine · 2025Article
- PD-1 interactome in osteosarcoma: identification of a novel PD-1/AXL interaction conserved between humans and dogs.Cell communication and signaling : CCS · 2024Article
- Tyrosine phosphataseFrontiers in immunology · 2024Review
- Targeting Aurora-A inhibits tumor progression and sensitizes thyroid carcinoma to Sorafenib by decreasing PFKFB3-mediated glycolysis.Cell death & disease · 2023Article
- Review
- Targeted therapy for head and neck cancer: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pharmacologic targeting of components of the MAPK/ERK pathway in differentiated thyroid carcinoma (DTC) is often limited due to the development of adaptive resistance. However, the detailed mechanism of MEK inhibitor (MEKi) resistance is not fully understood. Here, MEKi-resistant models were constructed successfully, in which multiple receptor tyrosine kinases (RTKs) signaling pathways and Src-homology 2 domain-containing phosphatase 2 (SHP2) were activated in MEKi-resistant cells. Given the physiological role of SHP2 as the downstream target of many RTKs, we first found blockade of SHP2 enhanced the sensitivity to MEKi in constructed MEKi-resistant models. Interestingly, we also found that compared with MEKi treatment alone, MEKi in combination with an SHP2 inhibitor markedly suppressed the reactivation of the MEK/ERK pathway; thus, the addition of the SHP2 inhibitor significantly improved the antitumor effects of MEKi. The synergistic suppression of DTC upon treatment with both inhibitors was further confirmed in xenograft models and transgenic models. Thus, our data suggest that RTKs activation leads to reactivation of the MAPK pathway and resistance to MEKi in DTC, which is reversed by SHP2 blockade. As a novel active inhibitor of SHP2, SHP099 in combination with MEKi is a promising therapeutic approach for advanced DTC and MEKi-resistant one.
Indexed as
Identifiers
35141016PMC8822290W4211266938What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.