ArticleFrontiers in pharmacology2022
SHP2 Inhibitors Show Anti-Myeloma Activity and Synergize With Bortezomib in the Treatment of Multiple Myeloma.
Article in Frontiers in pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 6 citations in OpenAlex.
- SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor.Reproduction (Cambridge, England) · 2023Article
- New prospectives on treatment opportunities in RASopathies.American journal of medical genetics. Part C, Seminars in medical genetics · 2022Review
- The Role of Small Heat Shock Proteins in Protein Misfolding Associated Motoneuron Diseases.International journal of molecular sciences · 2022Review
- Ajuforrestin A, an Abietane Diterpenoid fromMolecules (Basel, Switzerland) · 2022Article
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Authors and funding
9 authors at 4 institutions in 1 country.
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Abstract
Multiple myeloma (MM) is a plasma cell malignancy that remains incurable. The protein tyrosine phosphatase SHP2 is a central node regulating RAS/mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK) signaling pathway which plays a crucial role in the pathogenesis and proteasome inhibitor (PI) resistance of MM. Several preclinical studies have demonstrated that SHP2 inhibitors exerted antitumor activity in cancer-harboring diverse mutations in the RAS pathway, offering the potential for targeting myeloma. In this study, we showed that pharmacological inhibition of SHP2 activity using SHP099 and RMC-4550 efficiently inhibited the proliferation of MM cells by inducing apoptosis and cell cycle arrest. As per the mechanism, SHP2 inhibitors activated the level of cleaved caspase3, BAK, and P21 and downregulated ERK phosphorylation in MM cells. Moreover, the blockade of SHP2 exhibited anti-myeloma effect
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