ArticleCell reports. Medicine2025
Combined therapy with DR5-targeting antibody-drug conjugate and CDK inhibitors as a strategy for advanced colorectal cancer.
Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Emerging organoids and organoids-on-chip platforms for translational development of antibody‒drug conjugates and next-generation bioconjugates.Acta pharmaceutica Sinica. B · 2026Review
- Combined therapy with ALK inhibitors and a novel EGFR-targeting antibody‒drug conjugate as a strategy for ALK-rearranged non-small cell lung cancers.Oncogenesis · 2026Article
- Multidrug resistance in cancer: current understandings and future perspective.Molecular biomedicine · 2026Review
- Overcoming ADC resistance in advanced colorectal cancer by dual targeting of TROP2 and PERK to suppress Wnt/β-catenin signaling.Cell reports. Medicine · 2026Article
- Antibody-drug conjugates in colorectal cancer: advances in targeted delivery and personalized oncology.Frontiers in bioengineering and biotechnology · 2026Review
- Various machine learning prediction models for short-term postoperative prognosis of colorectal cancer based on intraoperative hypothermia.American journal of cancer research · 2026Article
- From mono- to multi-cellularFrontiers in cell and developmental biology · 2026Review
- A TROP2-targeting ADC synergizes with oxidative phosphorylation inhibitor to enhance apoptosis in ESCC by suppressing the PI3K-AKT-mTOR signaling pathway.Cell death & disease · 2025Article
- Mitochondrial metabolic reprogramming in colorectal cancer: mechanisms of resistance and future clinical interventions.Cell death discovery · 2025Review
- An overview of mechanisms, biomarkers, and treatment strategies for acquired anti-EGFR resistance in RAS wild-type colorectal cancer.Frontiers in pharmacology · 2025Review
- Antibody-drug conjugates as immuno-oncology agents in colorectal cancer: targets, payloads, and therapeutic synergies.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
19 authors.
Funding
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Abstract
Targeted therapies for advanced microsatellite stable (MSS) subtype colorectal cancer (MSS-CRC) remain a clinical challenge. Here, we show that death receptor 5 (DR5) is elevated in both MSS and microsatellite instability-high (MSI-H) colorectal cancer (CRC) cohorts, highlighting its potential as a clinical target. Oba01, a clinical-stage DR5-targeting antibody-drug conjugate (ADC) delivering the microtubule-disrupting agent monomethyl auristatin E (MMAE), shows superior efficacy in CRC cell lines, patient-derived xenografts and their corresponding organoids, irrespective of MSS or MSI-H status. Importantly, our functional multi-omics analysis reveals that the cell cycle pathway and cyclin-dependent kinases (CDKs) are key synergistic targets of Oba01's tumor-killing activity. We further show that Oba01 synergizes with the Food and Drug Administration (FDA)-approved CDK inhibitor abemaciclib in clinically relevant in vivo models. This synergy is also observed with other CDK inhibitors, underscoring the potential of combining Oba01 with CDK inhibition as a therapeutic strategy for advanced CRC, particularly the refractory MSS subtype.
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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.