ReviewOncogene2016
Stamping out RAF and MEK1/2 to inhibit the ERK1/2 pathway: an emerging threat to anticancer therapy.
Review in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
49 citing papers in PubMed, 89 citations in OpenAlex.
- Understanding hairy cell leukemia in the context of mature B-cell neoplasms: tumor microenvironment and extracellular vesicle contribution to disease pathogenesis.Frontiers in immunology · 2026Review
- TEAD4 Transcriptionally Activates TRIB3 to Induce Ferroptosis Resistance through the MEK/ERK Signaling Pathway in Colorectal Cancer.Gut and liver · 2025Article
- O-sialoglycoprotein Endopeptidase (OSGEP) Suppresses Hepatic Ischemia-Reperfusion Injury-Induced Ferroptosis Through Modulating the MEK/ERK Signaling Pathway.Molecular biotechnology · 2025Article
- Copper metabolism in hepatocellular carcinoma: from molecular mechanisms to therapeutic opportunities.Frontiers in molecular biosciences · 2025Review
- The Interplay between the DNA Damage Response (DDR) Network and the Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Multiple Myeloma.International journal of molecular sciences · 2024Review
- CircZCCHC2 decreases pirarubicin sensitivity and promotes triple-negative breast cancer development via the miR-1200/TPR axis.iScience · 2024Article
- Article
- Overexpression of CYP11A1 recovers cell cycle distribution in renal cell carcinoma Caki-1.Cancer cell international · 2022Article
- Amphioxus muscle transcriptomes reveal vertebrate-like myoblast fusion genes and a highly conserved role of insulin signalling in the metabolism of muscle.BMC genomics · 2022Article
- BRAF and MEK Inhibitors Affect Dendritic-Cell Maturation and T-Cell Stimulation.International journal of molecular sciences · 2021Article
- Immunomodulatory Properties of BRAF and MEK Inhibitors Used for Melanoma Therapy-Paradoxical ERK Activation and Beyond.International journal of molecular sciences · 2021Review
- TRERNA1 upregulation mediated by HBx promotes sorafenib resistance and cell proliferation in HCC via targeting NRAS by sponging miR-22-3p.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Revisiting Platinum-Based Anticancer Drugs to Overcome Gliomas.International journal of molecular sciences · 2021Review
- Targeting CDK9 for Anti-Cancer Therapeutics.Cancers · 2021Review
- How Does Endometriosis Lead to Ovarian Cancer? The Molecular Mechanism of Endometriosis-Associated Ovarian Cancer Development.Cancers · 2021Review
- Article
- Clinical Pharmacokinetics and Pharmacodynamics of Selumetinib.Clinical pharmacokinetics · 2021Review
- Response to re-challenge of a MEK inhibitor in a patient with recurrent low-grade serous carcinoma of the peritoneum.Gynecologic oncology reports · 2020Article
- Overview of current targeted therapy in gallbladder cancer.Signal transduction and targeted therapy · 2020Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The RAS-RAF-MEK1/2-ERK1/2 pathway is a key signal transduction pathway in the cells. Critically, it remains constitutively active in approximately 30% of human cancers, having key roles in cancer development, maintenance and progression, while being responsible for poorer prognosis and drug resistance. Consequently, the inhibition of this pathway has been the subject of intense research for >25 years. The advent of better patient screening techniques has increasingly shown that upstream regulators like RAS and RAF remain persistently mutated in many cancer types. These gain-of-function mutations, such as KRAS-4B(G12V/G13D/Q61K), NRAS(Q61L/Q61R) or BRAF(V600E), lead to tremendous increase in their activities, resulting in constitutively active extracellular signal-regulated kinase 1/2 (ERK1/2). They were not efficiently targeted by the first-generation inhibitors such as Lonafarnib or Sorafenib, which were essentially broad spectrum inhibitors targeting pan-RAS and pan-RAF, respectively. This triggered the development of the second-generation inhibitors selective against the mutated proteins. Second generation inhibitors such as Vemurafenib (Zelboraf) and Dabrafenib (Tafinlar) targeting BRAF(V600E), Trametinib (Mekinist) targeting MEK1/2 and the first generation pan-RAF inhibitor Sorafenib (Nexavar) have already been approved for treating renal, hepatocellular, thyroid cancers and BRAF(V600E/K) harboring metastatic melanoma. Others against RAF and MEK1/2 are presently undergoing clinical trials. Their success would depend on the better understanding of the acquired resistance mechanisms to these drugs in the cancer cells and the identification of predictive biomarkers for the proper administration of suitable inhibitor(s).
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What OpenQuestion 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 OpenQuestion graph.