ArticleeLife2017
MELK is not necessary for the proliferation of basal-like breast cancer cells.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed, 194 citations in OpenAlex.
- Exosomal export of activated CASPASE-8 is linked to the prevention of TNF-induced cytotoxicity.Nature communications · 2026Article
- Inhibition of ADSS2-mediated de novo AMP biosynthesis re-sensitizes acute myeloid leukemia to BH3 mimetics.Nature cancer · 2026Article
- Mechanisms and Design Principles of Proteolysis-Targeting Chimeras and Their Emerging Applications.ACS pharmacology & translational science · 2026Review
- VHL synthetic lethality screens uncover CBF-β as a negative regulator of STING.Nature communications · 2026Article
- Maternal Embryonic Leucine Zipper Kinase (Biology · 2026Review
- The role of MELK in cancer: mechanisms and therapeutic options.Frontiers in oncology · 2026Review
- PACT suppresses PKR activation through dsRNA binding and dimerization, and is a therapeutic target for triple-negative breast cancer.RNA (New York, N.Y.) · 2025Article
- Targeting MELK in tumor cells and tumor microenvironment: from function and mechanism to therapeutic application.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Germline Single-Nucleotide PolymorphismBiomedicines · 2025Article
- Maternal Embryonic Leucine Zipper Kinase (MELK) as a Promising Therapeutic Target in Triple Negative Breast Cancer.Anti-cancer agents in medicinal chemistry · 2025Review
- Redirecting E3 ubiquitin ligases for targeted protein degradation with heterologous recognition domains.The Journal of biological chemistry · 2025Article
- Histone demethylase enzymes KDM5A and KDM5B modulate immune response by suppressing transcription of endogenous retroviral elements.bioRxiv : the preprint server for biology · 2024Article
- Discovery of first-in-class PROTACs targeting maternal embryonic leucine zipper kinase (MELK) for the treatment of Burkitt lymphoma.RSC medicinal chemistry · 2024Article
- Tumor cell-intrinsic MELK enhanced CCL2-dependent immunosuppression to exacerbate hepatocarcinogenesis and confer resistance of HCC to radiotherapy.Molecular cancer · 2024Article
- A Tandem-Affinity Purification Method for Identification of Primary Intracellular Drug-Binding Proteins.ACS chemical biology · 2024Article
- Spatiotemporal regulation of MELK during mitosis.Frontiers in cell and developmental biology · 2024Article
- Innovative therapeutic strategies to overcome radioresistance in breast cancer.Frontiers in oncology · 2024Review
- EZH2 K63-polyubiquitination affecting migration in extranodal natural killer/T-cell lymphoma.Clinical epigenetics · 2023Article
- Inhibition of a lower potency target drives the anticancer activity of a clinical p38 inhibitor.Cell chemical biology · 2023Article
- Precision Oncology Comes of Age: Designing Best-in-Class Small Molecules by Integrating Two Decades of Advances in Chemistry, Target Biology, and Data Science.Cancer discovery · 2023Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
Thorough preclinical target validation is essential for the success of drug discovery efforts. In this study, we combined chemical and genetic perturbants, including the development of a novel selective maternal embryonic leucine zipper kinase (MELK) inhibitor HTH-01-091, CRISPR/Cas9-mediated MELK knockout, a novel chemical-induced protein degradation strategy, RNA interference and CRISPR interference to validate MELK as a therapeutic target in basal-like breast cancers (BBC). In common culture conditions, we found that small molecule inhibition, genetic deletion, or acute depletion of MELK did not significantly affect cellular growth. This discrepancy to previous findings illuminated selectivity issues of the widely used MELK inhibitor OTSSP167, and potential off-target effects of MELK-targeting short hairpins. The different genetic and chemical tools developed here allow for the identification and validation of any causal roles MELK may play in cancer biology, which will be required to guide future MELK drug discovery efforts. Furthermore, our study provides a general framework for preclinical target validation.
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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.