ArticleNature chemical biology2019
CRISPR-Cas9 screens identify regulators of antibody-drug conjugate toxicity.
Article in Nature chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 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
46 citing papers in PubMed, 82 citations in OpenAlex.
- Antibody-drug conjugate engineering: from design to efficacy and safety.Signal transduction and targeted therapy · 2026Review
- Programmed cell death and metastatic evolution in breast cancer: the role of anoikis, necroptosis, and ferroptosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Pan-cancer multi-omic integration of Trop2 reveals biological determinants and translational implications for ADC therapy.NPJ precision oncology · 2026Article
- Understanding and Overcoming Antibody-Drug Conjugate Resistance: Biological Mechanisms and Emerging Analytical Frameworks in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Unveiling the molecular and immunological drivers of antibody-drug conjugates in cancer treatment.Nature reviews. Cancer · 2025Review
- Applications of Genome-wide Screening of CRISPR/Cas9 Knockout Library in Identifying Novel Molecular Targets for Xenobiotics.Environment & health (Washington, D.C.) · 2025Review
- A genome-wide CRISPR screen unveils the endosomal maturation protein WDR91 as a promoter of productive ASO activity in melanoma.Molecular therapy. Nucleic acids · 2025Article
- Comparison of Current Immunotherapy Approaches and Novel Anti-Cancer Vaccine Modalities for Clinical Application.International journal of molecular sciences · 2025Review
- CRISPR screening approaches in breast cancer research.Cancer metastasis reviews · 2025Review
- The Tumour Glyco-Code: Sialylation as a Mediator of Stromal Cell Immunosuppression in the Tumour Microenvironment.European journal of immunology · 2025Review
- Expanding the potential of antibody-drug conjugates in gastrointestinal malignancies: beyond HER2 targets.ESMO gastrointestinal oncology · 2025Review
- CRISPR screens with trastuzumab emtansine in HER2-positive breast cancer cell lines reveal new insights into drug resistance.Breast cancer research : BCR · 2025Article
- FORCE platform overcomes barriers of oligonucleotide delivery to muscle and corrects myotonic dystrophy features in preclinical models.Communications medicine · 2025Article
- New insights into the immunomodulatory potential of sialic acid on monocyte-derived dendritic cells.Cancer immunology, immunotherapy : CII · 2024Article
- CRISPR/Cas9 technology for advancements in cancer immunotherapy: from uncovering regulatory mechanisms to therapeutic applications.Experimental hematology & oncology · 2024Review
- Bispecific antibody drug conjugates: Making 1+1>2.Acta pharmaceutica Sinica. B · 2024Review
- Drug conjugates for the treatment of lung cancer: from drug discovery to clinical practice.Experimental hematology & oncology · 2024Review
- GMP-manufactured CRISPR/Cas9 technology as an advantageous tool to support cancer immunotherapy.Journal of experimental & clinical cancer research : CR · 2024Review
- Antibody-drug conjugates in cancer therapy: innovations, challenges, and future directions.Archives of pharmacal research · 2024Review
- Antibody-drug conjugates come of age in oncology.Nature reviews. Drug discovery · 2023Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Antibody-drug conjugates (ADCs) selectively deliver chemotherapeutic agents to target cells and are important cancer therapeutics. However, the mechanisms by which ADCs are internalized and activated remain unclear. Using CRISPR-Cas9 screens, we uncover many known and novel endolysosomal regulators as modulators of ADC toxicity. We identify and characterize C18ORF8/RMC1 as a regulator of ADC toxicity through its role in endosomal maturation. Through comparative analysis of screens with ADCs bearing different linkers, we show that a subset of late endolysosomal regulators selectively influence toxicity of noncleavable linker ADCs. Surprisingly, we find cleavable valine-citrulline linkers can be processed rapidly after internalization without lysosomal delivery. Lastly, we show that sialic acid depletion enhances ADC lysosomal delivery and killing in diverse cancer cell types, including with FDA (US Food and Drug Administration)-approved trastuzumab emtansine (T-DM1) in Her2-positive breast cancer cells. Together, these results reveal new regulators of endolysosomal trafficking, provide important insights for ADC design and identify candidate combination therapy targets.
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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.