ArticleCancer biology & medicine2019
Synergistic inhibition of MEK and reciprocal feedback networks for targeted intervention in malignancy.
Article in Cancer biology & medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- The SOS1 Inhibitor BI 1701963 as Monotherapy or in Combination with Trametinib in Patients with KRAS Mutation-Positive Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Targeting the MAPK Pathway in Cancer.International journal of molecular sciences · 2025Review
- Article
- Practical immunomodulatory landscape of glioblastoma multiforme (GBM) therapy.Journal of the Egyptian National Cancer Institute · 2024Review
- Interdependency and differential expression of ERK1 and ERK2 in breast and melanoma cell lines.Journal of the Egyptian National Cancer Institute · 2024Article
- Regulation of MEK inhibitor selumetinib sensitivity by AKT phosphorylation in the novel BRAF L525R mutant.International journal of clinical oncology · 2023Article
- New Directions in the Therapy of Glioblastoma.Cancers · 2022Review
- Review
- Step-by-step comparison of ordinary differential equation and agent-based approaches to pharmacokinetic-pharmacodynamic models.CPT: pharmacometrics & systems pharmacology · 2022Article
- Protease-triggered bioresponsive drug delivery for the targeted theranostics of malignancy.Acta pharmaceutica Sinica. B · 2021Review
- Everything Old Is New Again: Drug Repurposing Approach for Non-Small Cell Lung Cancer Targeting MAPK Signaling Pathway.Frontiers in oncology · 2021Review
- The Latest on Uveal Melanoma Research and Clinical Trials: Updates from the Cure Ocular Melanoma (CURE OM) Science Meeting (2019).Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Magnetic resonance imaging-guided and targeted theranostics of colorectal cancer.Cancer biology & medicine · 2020Review
- Loss of HAT1 expression confers BRAFV600E inhibitor resistance to melanoma cells by activating MAPK signaling via IGF1R.Oncogenesis · 2020Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The RAS-RAF-MEK-ERK signaling pathway (MAPK signaling pathway) plays a significant role in multiple pathological behaviors and is most frequently dysregulated in more than 30% of human cancers. As key elements in this pathway, MEK1/2 play crucial roles in tumorigenesis and the inhibition of apoptosis, which makes their inhibition an attractive antitumor strategy. Dozens of potent non-ATP-competitive allosteric MEK1/2 inhibitors have been developed that have produced substantial improvement in clinical outcomes over the past decade. However, the efficacy of these agents is limited, and response rates are variable in a wide range of tumors that harbor RAS and RAF mutations due to the development of resistance, which is derived mainly from the persistence of MAPK signaling and increased activation of the mutual feedback networks. Both intrinsic and acquired resistance to MEK inhibitors necessitates the synergistic targeting of both pathways to restore the therapeutic effects of a single agent. In this review, the significant role of the MAPK pathway in carcinogenesis and its therapeutic potential are comprehensively examined with a focus on MEK inhibitors. Then, the activation of feedback networks accompanying MEK inhibition is briefly reviewed. Combination strategies that involve the simultaneous inhibition of the original and resistance pathways are highlighted and elaborately described on the basis of the latest research progress. Finally, the obstacles to the development of MEK-related combination systems are discussed in order to lay the groundwork for their clinical application as frontline treatments for individual patients with MAPK-hyperactivated malignancies.
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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 OpenQuestion graph.