ArticleThe American journal of pathology2013
Identification of aurora kinase B and Wee1-like protein kinase as downstream targets of (V600E)B-RAF in melanoma.
Article in The American journal of pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- An update of predictive biomarkers related to WEE1 inhibition in cancer therapy.Journal of cancer research and clinical oncology · 2024Pooled it
- Functional screening reveals genetic dependencies and diverging cell cycle control in atypical teratoid rhabdoid tumors.Genome biology · 2024Article
- WEE1 Inhibitor Adavosertib Exerts Antitumor Effects on Colorectal Cancer, Especially in Cases withCancers · 2024Article
- Genome-wide analyses reveals an association between invasive urothelial carcinoma in the Shetland sheepdog and NIPAL1.NPJ precision oncology · 2024Article
- Targeting WEE1/AKT Restores p53-Dependent Natural Killer-Cell Activation to Induce Immune Checkpoint Blockade Responses in "Cold" Melanoma.Cancer immunology research · 2022Article
- Novel Therapeutic Approaches with DNA Damage Response Inhibitors for Melanoma Treatment.Cells · 2022Review
- Targeting BRAF V600E in metastatic colorectal cancer: where are we today?Ecancermedicalscience · 2022Review
- BRAFeLife · 2021Article
- Host-Parasite Interaction of Atlantic salmon (Frontiers in immunology · 2021Article
- Management ofFrontiers in oncology · 2021Review
- Loss of miR-155 upregulates WEE1 in metastatic melanoma.Melanoma research · 2019Article
- Kinase inhibitor library screening identifies synergistic drug combinations effective in sensitive and resistant melanoma cells.Journal of experimental & clinical cancer research : CR · 2019Article
- Vitamin C Prevents Ultraviolet-induced Pigmentation in Healthy Volunteers: Bayesian Meta-analysis Results from 31 Randomized Controlled versus Vehicle Clinical Studies.The Journal of clinical and aesthetic dermatology · 2019Article
- Nanoliposomal delivery of cytosolic phospholipase ANanomedicine : nanotechnology, biology, and medicine · 2018Article
- Moving Synergistically Acting Drug Combinations to the Clinic by Comparing Sequential versus Simultaneous Drug Administrations.Molecular pharmacology · 2018Article
- Kinase-targeted cancer therapies: progress, challenges and future directions.Molecular cancer · 2018Review
- Identification of WEE1 as a target to make AKT inhibition more effective in melanoma.Cancer biology & therapy · 2018Article
- Improving pharmacological targeting of AKT in melanoma.Cancer letters · 2017Article
- Identifying the structure-activity relationship of leelamine necessary for inhibiting intracellular cholesterol transport.Oncotarget · 2017Article
- Nanoparticle-Based Celecoxib and Plumbagin for the Synergistic Treatment of Melanoma.Molecular cancer therapeutics · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 3 countries.
Funding
Abstract
BRAF is the most mutated gene in melanoma, with approximately 50% of patients containing V600E mutant protein. (V600E)B-RAF can be targeted using pharmacological agents, but resistance develops in patients by activating other proteins in the signaling pathway. Identifying downstream members in this signaling cascade is important to design strategies to avoid the development of resistance. Unfortunately, downstream proteins remain to be identified and therapeutic potential requires validation. A kinase screen was undertaken to identify downstream targets in the (V600E)B-RAF signaling cascade. Involvement of aurora kinase B (AURKB) and Wee1-like protein kinase (WEE1) as downstream proteins in the (V600E)B-RAF pathway was validated in xenografted tumors, and mechanisms of action were characterized in size- and time-matched tumors. Levels of only AURKB and WEE1 decreased in melanoma cells, when (V600E)B-RAF, mitogen-activated protein kinase 1/2, or extracellular signal-regulated kinase 1/2 protein levels were reduced using siRNA compared with other identified kinases. AURKB and WEE1 were expressed in tumors of patients with melanoma at higher levels than observed in normal human melanocytes. Targeting these proteins reduced tumor development by approximately 70%, similar to that observed when inhibiting (V600E)B-RAF. Furthermore, protein or activity levels of AURKB and WEE1 decreased in melanoma cells when pharmacological agents targeting upstream (V600E)B-RAF or mitogen-activated protein kinase were used to inhibit the (V600E)B-RAF pathway. Thus, AURKB and WEE1 are targets and biomarkers of therapeutic efficacy, lying downstream of (V600E)B-RAF in melanomas.
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Registered trials
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