ArticleNature2012
Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 668 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
668 citing papers in PubMed, 1,105 citations in OpenAlex.
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- Population Pharmacokinetics of MCLA-128, a HER2/HER3 Bispecific Monoclonal Antibody, in Patients with Solid Tumors.Clinical pharmacokinetics · 2020Trial
- Advancing antibody drug conjugates in gastrointestinal cancers.British journal of cancer · 2026Review
- High-throughput spheroid profiling reveals BMP-driven rewiring of glioma cell death responses.bioRxiv : the preprint server for biology · 2026Article
- Antibody-Drug Conjugates in Lung Cancer: Promise, Progress, and Persistent Challenges.Current issues in molecular biology · 2026Review
- AXL phosphosite mapping links FAK1 and YAP1 signaling to erlotinib resistance in EGFR-mutant lung cancer.Cell reports · 2026Article
- Multifactorial sheltering in peristromal niches shapes in vivo responses of lung cancers to targeted therapies.Nature communications · 2026Article
- Recurrent cancer-associated ERBB4 mutations are transforming and confer resistance to targeted therapies.Molecular oncology · 2026Article
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- Covalent inhibitor design confers activity against both GDP- and GTP-bound forms of KRAS G12C.Nature communications · 2026Article
- Growth factors maintain intratumoral heterogeneity and drive therapeutic resistance in triple-negative breast cancer.Cell reports · 2026Article
- Article
- Paired single cell analysis reveals chemotherapy resistance in osteosarcoma.Cancer drug resistance (Alhambra, Calif.) · 2026Article
- Overcoming resistance to antibody-drug conjugates: from mechanistic insights to cutting-edge strategies.Journal of hematology & oncology · 2025Review
- Synthesis, Anticancer Evaluation, and Molecular Docking of Novel Thiazolobenzimidazole-Thiazole Hybrids as Potent Colon Cancer Inhibitors.ChemistryOpen · 2025Article
- Targeting mesenchymal-epithelial transition factor signaling in cancer: from genetic alterations to clinical advances and future prospects.Molecular biology reports · 2025Review
- The Role of Mesenchymal Stem Cells in Drug Resistance in Lung Neoplasms.Journal of cancer prevention · 2025Review
- Ti-Based Metallic Biomaterials for Antitumor Applications.Materials (Basel, Switzerland) · 2025Review
608 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
Mutationally activated kinases define a clinically validated class of targets for cancer drug therapy. However, the efficacy of kinase inhibitors in patients whose tumours harbour such alleles is invariably limited by innate or acquired drug resistance. The identification of resistance mechanisms has revealed a recurrent theme—the engagement of survival signals redundant to those transduced by the targeted kinase. Cancer cells typically express multiple receptor tyrosine kinases (RTKs) that mediate signals that converge on common critical downstream cell-survival effectors—most notably, phosphatidylinositol-3-OH kinase (PI(3)K) and mitogen-activated protein kinase (MAPK). Consequently, an increase in RTK-ligand levels, through autocrine tumour-cell production, paracrine contribution from tumour stroma or systemic production, could confer resistance to inhibitors of an oncogenic kinase with a similar signalling output. Here, using a panel of kinase-'addicted' human cancer cell lines, we found that most cells can be rescued from drug sensitivity by simply exposing them to one or more RTK ligands. Among the findings with clinical implications was the observation that hepatocyte growth factor (HGF) confers resistance to the BRAF inhibitor PLX4032 (vemurafenib) in BRAF-mutant melanoma cells. These observations highlight the extensive redundancy of RTK-transduced signalling in cancer cells and the potentially broad role of widely expressed RTK ligands in innate and acquired resistance to drugs targeting oncogenic kinases.
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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.