ArticleeLife2017
CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 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
91 citing papers in PubMed.
- Targeted Nanoparticle Delivery CRISPR/Cas9: overcoming biological barriers, enhancing stability, and improving therapeutic precision.International journal of pharmaceutics: X · 2026Review
- Drugging non-canonical kinases in cancer therapeutics: Molecular targets, underlying mechanisms and small-molecule inhibitors.Acta pharmaceutica Sinica. B · 2026Review
- Review
- Maternal Embryonic Leucine Zipper Kinase (Biology · 2026Review
- The role of MELK in cancer: mechanisms and therapeutic options.Frontiers in oncology · 2026Review
- Challenges and opportunities for oncology drug repurposing informed by synthetic lethality.NPJ systems biology and applications · 2025Article
- FTO depletion does not alter mbioRxiv : the preprint server for biology · 2025Article
- Large language models for drug discovery and development.Patterns (New York, N.Y.) · 2025Review
- PI5P4K inhibitors: promising opportunities and challenges.The FEBS journal · 2025Review
- The immortality mechanism of TERT promoter mutant cancers is self-reinforcing and reversible.Molecular cell · 2025Article
- A heterogeneous pharmaco-transcriptomic landscape induced by targeting a single oncogenic kinase.bioRxiv : the preprint server for biology · 2025Article
- Crip2 affects vascular development by fine-tuning endothelial cell aggregation and proliferation.Cellular and molecular life sciences : CMLS · 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
- The multiple functions and mechanisms of long non-coding RNAs in regulating breast cancer progression.Frontiers in pharmacology · 2025Review
- Melk facilitates pulmonary artery smooth muscle cell proliferation and migration in pulmonary hypertension via modulation of YAP/TAZ signaling.Frontiers in cell and developmental biology · 2025Article
- PRMT1 inhibition perturbs RNA metabolism and induces DNA damage in clear cell renal cell carcinoma.Nature communications · 2024Article
- High-resolution genome-wide mapping of chromosome-arm-scale truncations induced by CRISPR-Cas9 editing.Nature genetics · 2024Article
- Targeting MELK improves PD-1 blockade efficiency in cervical cancer via enhancing antitumor immunity.Molecular therapy. Oncology · 2024Article
- Spatiotemporal regulation of MELK during mitosis.Frontiers in cell and developmental biology · 2024Article
- PIM kinases regulate early human Th17 cell differentiation.Cell reports · 2023Article
31 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
4 authors.
Funding
Abstract
The Maternal Embryonic Leucine Zipper Kinase (MELK) has been reported to be a genetic dependency in several cancer types. MELK RNAi and small-molecule inhibitors of MELK block the proliferation of various cancer cell lines, and MELK knockdown has been described as particularly effective against the highly-aggressive basal/triple-negative subtype of breast cancer. Based on these preclinical results, the MELK inhibitor OTS167 is currently being tested as a novel chemotherapy agent in several clinical trials. Here, we report that mutagenizing MELK with CRISPR/Cas9 has no effect on the fitness of basal breast cancer cell lines or cell lines from six other cancer types. Cells that harbor null mutations in MELK exhibit wild-type doubling times, cytokinesis, and anchorage-independent growth. Furthermore, MELK-knockout lines remain sensitive to OTS167, suggesting that this drug blocks cell division through an off-target mechanism. In total, our results undermine the rationale for a series of current clinical trials and provide an experimental approach for the use of CRISPR/Cas9 in preclinical target validation that can be broadly applied.
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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.