ArticleApoptosis : an international journal on programmed cell death2024
Targeted delivery of FAK siRNA by engineered exosomes to reverse cetuximab resistance via activating paraptosis in colon cancer.
Article in Apoptosis : an international journal on programmed cell death, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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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
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Global research landscape and hotspots of paraptosis: a multi-database bibliometric analysis with a focused literature review.Frontiers in oncology · 2026Pooled it
- Exosome-Based Drug Delivery Systems in Colorectal Cancer: Current Evidence and Future Perspectives.The AAPS journal · 2026Review
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
- Exosome-mediated siRNA delivery in cancer: Loading strategies, targeting approaches, and therapeutic outcomes.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Review
- Engineered small extracellular vesicles as bioactive materials: Integrating engineering strategies for cargo loading and targeted delivery systems.Bioactive materials · 2026Review
- Crosstalk Between Autophagy and Paraptosis: A New Frontier in Cancer Therapy.International journal of molecular sciences · 2026Review
- A multidimensional landscape of extracellular vesicle-mediated tumor drug resistance: mechanisms, biomarkers, engineered drug delivery, and clinical translation.Extracellular vesicles and circulating nucleic acids · 2026Review
- Engineering Small Extracellular Vesicles for Colon-Targeted Delivery: Microenvironment-Responsive Design, Therapeutic Mechanisms, and Clinical Translation.International journal of nanomedicine · 2026Review
- Paraptosis-related genes regulate tumor immune microenvironment and predict prognosis in breast cancer.Journal of cell communication and signaling · 2025Article
- pH-responsive biomimetic zeolitic imidazolate framework-based nanoparticles for co-delivery of cetuximab and siRNA in synergistic therapy of laryngeal squamous cell carcinoma.Journal of pharmaceutical analysis · 2025Article
- Exosomal long noncoding RNAs and microRNAs in colorectal cancer.Tzu chi medical journalReview
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
backgroundCetuximab is extensively used in the treatment of metastatic colorectal cancer (mCRC). However, resistance poses a significant challenge to successful therapy. Recently, paraptosis, a non-classical programmed cell death, has garnered increased attention for its potential application value in antitumor treatments. We aimed to identify the essential pathways and signaling molecules involved in paraptosis inhibition and select them as therapeutic targets in cetuximab resistance. Additionally, engineered exosome technology is used as a drug delivery system with both targeted and effector properties.
resultsBy comparing the differential expression of paraptosis-related genes between drug-resistant colon cancer cells and sensitive cells, it was observed that the paraptosis level induced by cetuximab was significantly downregulated in drug-resistant cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified the focal adhesion kinase (FAK) signaling pathway as a key pathway involved in the suppression of paraptosis. The biological function of FAK in cetuximab-resistant cells was investigated through cell morphology observation, CCK-8 assay, colony formation assay, RT-qPCR, Western Blot, and loss-of-function experiments. The results showed that the FAK signaling pathway was significantly upregulated in cetuximab-resistant colon cancer cells, and siRNA interference targeting FAK could notably inhibit cell proliferation while upregulating the paraptosis level. Based on this, engineered colon cancer cells targeted and FAK siRNA loaded exosomes (CT-Exo-siFAK1) were constructed. In vitro experiments, CT-Exo-siFAK1 could effectively activate paraptosis and inhibit the proliferation of drug-resistant colon cancer cells. In vivo experiments also confirmed that CT-Exo-siFAK1 significantly suppressed tumor growth and metastasis while upregulating the paraptosis level.
conclusionThis study suggests that FAK signaling pathway-mediated inhibition of paraptosis levels is crucial in the sensitivity of cetuximab targeted therapy in colon cancer, and the use of engineered exosomes to deliver FAK siRNA may be an effective strategy to reverse cetuximab resistance.
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