ArticleiScience2025
Targeting FAK improves the tumor uptake of antibody-drug conjugates to strengthen the anti-cancer responses.
Article in iScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- The 2024 Lebanon conflict: a multidimensional assessment of syndemic impacts on public health and sustainable development goals.Internal and emergency medicine · 2026Review
- Bacteria-nanoplastic interactions: mechanisms, ecological consequences, and advances in biodegradation technologies.Archives of microbiology · 2026Review
- A metabolomic clock of population ageing: cross-cohort validation and associations with frailty and cognitive function.GeroScience · 2026Article
- DNA/RNA Methylation-Driven Coronary Microvascular Dysfunction: Emerging Pathogenic Mechanisms and Therapeutic Opportunities for Heart Failure in Diabetes.Cardiovascular drugs and therapy · 2026Review
- A Comprehensive Review on CRISPR-Based Screening and Its Applications.Molecular biotechnology · 2026Review
- Collagen-derived biomarkers reveal distinct fibrotic responses among cancer-associated fibroblasts.Scientific reports · 2026Article
- When effective anticancer therapies are, in fact, destabilizing the tumor's Group Phenotypic Composition.NPJ precision oncology · 2026Review
- Understanding and Overcoming Antibody-Drug Conjugate Resistance: Biological Mechanisms and Emerging Analytical Frameworks in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Current advances in immunotherapy for KRAS-Mutant pancreatic cancer.Clinical and experimental medicine · 2026Review
- Insights into the mechanism, selectivity, solvent, and temperature effect in the Diels-Alder reactions of 2,5-bis(hydroxymethyl)furan and maleimides derivatives leading to anticancer norcantharimide derivatives: an MEDT study.Journal of molecular modeling · 2026Article
- Capsule enclosed coordinate attention based dual batch depthwise convolutional knowledge distillation model for drug-drug interaction prediction.Molecular diversity · 2026Article
- Disarming cancer resistance: FAK as a therapeutic target.Trends in cancer · 2026Review
- Atorvastatin regulates hepatic transcriptome PXR dependently but distinct from pregnenolone 16α-carbonitrile and does not induce PXR-mediated liver steatosis.Archives of toxicology · 2026Article
- Mechanisms of Resistance and Synergy: The Role of Tumor Microenvironment in HER2-Low Breast Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- FAK inhibition in ovarian cancer releases omega-3 fatty acids to program CXCL13-producing anti-tumor resident peritoneal macrophages.Cell reports · 2026Article
- Cellular lipids: fundamental host factors for monkeypox virus replication and pathogenesis.Archives of microbiology · 2026Review
- Glioblastoma exosomes reprogramming the tumor microenvironment and evading therapeutic challenges.Molecular biology reports · 2026Review
- Provoking myofibroblast death: Strategies to resolve fibrosis and remodel tumor microenvironment.World journal of clinical oncology · 2025Review
- Intermodulation of endoplasmic reticulum stress and ferroptosis in diabetic nephropathy: molecular mechanisms and therapeutic potentials.Apoptosis : an international journal on programmed cell death · 2025Review
- Harnessing cuproptosis: a new avenue for targeted cancer therapies.Apoptosis : an international journal on programmed cell death · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibody-drug conjugates (ADCs), exemplified by HER2-targeted Enhertu and TROP2-targeted Trodelvy, have demonstrated significant therapeutic potential in cancers. However, a subset of patients remains refractory to ADC treatment, suggesting that the efficacy requires further optimization. Here, we demonstrate that excessive cancer-associated fibroblasts (CAFs) can form a fibrotic barrier, impeding the tissue uptake of ADCs to dampen the anti-tumor efficacy. Mechanistically, cancer cells transform normal fibroblasts into FAK-activated CAFs. The proliferation of these CAFs reduces the tumor uptake of macromolecular drugs, conferring resistance to ADCs. Targeting FAK with a small molecule inhibitor IN10018 effectively diminishes the CAF-associated tumor barrier, enhancing the tumor uptake of various ADCs irrespective of their specific targets. Combination therapy with IN10018 and ADCs targeting either HER2 or TROP2 consistently yielded superior antitumor outcomes compared to monotherapies in animal models. These findings provide compelling preclinical evidence supporting the clinical evaluation of IN10018 in combination with ADCs.
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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 Socratic graph.