ArticleNPJ precision oncology2023
Chemoresistant fibroblasts dictate neoadjuvant chemotherapeutic response of head and neck cancer via TGFα-EGFR paracrine signaling.
Article in NPJ precision oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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Who cites it
11 citing papers in PubMed, 10 citations in OpenAlex.
- Ras homolog family member A expression is associated with reduced cetuximab sensitivity in head and neck squamous cell carcinoma.The Journal of international medical research · 2026Article
- Cancer-associated fibroblasts as a target in head and neck squamous cell carcinoma: bridging mechanisms to therapy with drugs, adjuvants, and nanotechnology.Discover oncology · 2026Review
- A Head and Neck Cancer Patient-Specific Microphysiological System for Predicting Response to Chemoradiation.bioRxiv : the preprint server for biology · 2026Article
- The research advances of crosstalk between cancer-associated fibroblasts and tumor cells using co-culture organoids.Cell death & disease · 2026Review
- [Research and application progress of organoids in head and neck squamous cell carcinoma].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2026Review
- EMT and cancer stem cells: Drivers of therapy resistance and promising therapeutic targets.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2025Review
- Establishment of a chemoresistant laryngeal cancer cell model to study chemoresistance and chemosensitization responses via transcriptomic analysis and a tumor-on-a-chip platform.Bioengineering & translational medicine · 2025Article
- Pancreatic Cancer: Pathogenesis and Clinical Studies.MedComm · 2025Review
- Organoid Technology in Precision Medicine for Head and Neck Cancer.Oncology research · 2025Review
- Molecular insights into immune evasion in head and neck squamous cell carcinomas: Toward a promising treatment strategy.Oncology research · 2025Review
- Pericytes Modulate Third-Generation Tyrosine Kinase Inhibitor Sensitivity in EGFR-Mutated Lung Cancer Cells Through IL32-β5-Integrin Paracrine Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Conventional chemotherapy targets malignant cells without evaluating counter protection from the tumor microenvironment that often causes treatment failure. Herein, we establish chemoresistant fibroblasts (rCAFs) as regulators of neoadjuvant chemotherapeutic (NACT) response in head and neck squamous cell carcinoma (HNSCC). Clinically, high expression of CAF-related gene signature correlates with worse prognosis and chemotherapeutic response in multiple cancers, while the population of CAFs in the residual tumors of chemoresistant HNSCC patients remains unchanged after NACT treatment, compared to chemosensitive patients. Using a murine cancer model or patient-derived organoid, and primary CAFs isolated from chemo-sensitive (sCAFs) or -resistant patients, we show that rCAFs, but not sCAFs, are resistant to chemotherapy-induced apoptosis while reducing HNSCC cell chemosensitivity via paracrine signals. Combined multi-omics and biochemical analyses indicate an elevated PI3K/AKT/p65 driven cell survival and cytokine production in rCAFs, while rCAF-secreted TGFα promotes cancer cell chemoresistance by activating EGFR/Src/STAT3 survival signaling axis. Treatment with anti-EGFR cetuximab restores the chemosensitivity of tumors derived from co-injection of cancer cells and rCAFs in vivo, while the serum level of TGFα determines NACT response in HNSCC patients. Overall, our findings uncover a novel insight whereby the crosstalk between tumor cell and rCAF determines chemotherapeutic response and prognosis in cancer patients.
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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.