ReviewNaunyn-Schmiedeberg's archives of pharmacology2014
A comprehensive review of the preclinical efficacy profile of the ErbB family blocker afatinib in cancer.
Review in Naunyn-Schmiedeberg's archives of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 109 citations in OpenAlex.
- Article
- Advancements in Targeted Therapies for Colorectal Cancer: Overcoming Challenges and Exploring Future Directions.Cancers · 2025Review
- The differentiation state of small intestinal organoid models influences prediction of drug-induced toxicity.Frontiers in cell and developmental biology · 2025Article
- Imidazole[1,5-a]pyridine derivatives as EGFR tyrosine kinase inhibitors unraveled by umbrella sampling and steered molecular dynamics simulations.Scientific reports · 2024Article
- Nephrotoxicity of targeted therapy used to treat lung cancer.Frontiers in immunology · 2024Review
- Epigenetic regulation in lung cancer.MedComm · 2023Review
- Variational autoencoder-based chemical latent space for large molecular structures with 3D complexity.Communications chemistry · 2023Article
- How many kinases are druggable? A review of our current understanding.The Biochemical journal · 2023Article
- Therapeutic approaches for the treatment of head and neck squamous cell carcinoma-An update on clinical trials.Translational oncology · 2022Review
- Synergistic cytotoxicity of the CDK4 inhibitor Fascaplysin in combination with EGFR inhibitor Afatinib against Non-small Cell Lung Cancer.Investigational new drugs · 2022Article
- The Yin and Yang of ERBB4: Tumor Suppressor and Oncoprotein.Pharmacological reviews · 2022Review
- Globally Approved EGFR Inhibitors: Insights into Their Syntheses, Target Kinases, Biological Activities, Receptor Interactions, and Metabolism.Molecules (Basel, Switzerland) · 2021Review
- Bypassing P-glycoprotein mediated efflux of afatinib by cyclodextrin complexation - Evaluation of intestinal absorption and anti-cancer activity.Journal of molecular liquids · 2021Article
- Progress in the Research and Targeted Therapy of ErbB/HER Receptors in Urothelial Bladder Cancer.Frontiers in molecular biosciences · 2021Review
- The guanine nucleotide exchange factor VAV3 participates in ERBB4-mediated cancer cell migration.The Journal of biological chemistry · 2020Article
- How Different Substitution Positions of F, Cl Atoms in Benzene Ring of 5-Methylpyrimidine Pyridine Derivatives Affect the Inhibition Ability of EGFRMolecules (Basel, Switzerland) · 2020Article
- Constitutive or Induced HIF-2 Addiction is Involved in Resistance to Anti-EGFR Treatment and Radiation Therapy in HNSCC.Cancers · 2019Article
- Controlling ERK Activation Dynamics in Mammary Epithelial Cells with Alternating Electric Fields through Microelectrodes.Nano letters · 2019Article
- Design and synthesis of novel 6-substituted quinazoline-2-thiols.Molecular diversity · 2019Article
- Clinical development of targeted and immune based anti-cancer therapies.Journal of experimental & clinical cancer research : CR · 2019Review
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Afatinib (also known as BIBW 2992) has recently been approved in several countries for the treatment of a distinct type of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer. This manuscript comprehensively reviews the preclinical data on afatinib, an irreversible inhibitor of the tyrosine kinase activity of members of the epidermal growth factor receptor family (ErbB) including EGFR, HER2 and ErbB4. Afatinib covalently binds to cysteine 797 of the EGFR and the corresponding cysteines 805 and 803 in HER2 and ErbB4, respectively. Such covalent binding irreversibly inhibits the tyrosine kinase activity of these receptors, resulting in reduced auto- and transphosphorylation within the ErbB dimers and inhibition of important steps in the signal transduction of all ErbB receptor family members. Afatinib inhibits cellular growth and induces apoptosis in a wide range of cells representative for non-small cell lung cancer, breast cancer, pancreatic cancer, colorectal cancer, head and neck squamous cell cancer and several other cancer types exhibiting abnormalities of the ErbB network. This translates into tumour shrinkage in a variety of in vivo rodent models of such cancers. Afatinib retains inhibitory effects on signal transduction and in vitro and in vivo cancer cell growth in tumours resistant to reversible EGFR inhibitors, such as those exhibiting the T790M mutations. Several combination treatments have been explored to prevent and/or overcome development of resistance to afatinib, the most promising being those with EGFR- or HER2-targeted antibodies, other tyrosine kinase inhibitors or inhibitors of downstream signalling molecules.
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What OpenQuestion holds
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.