ReviewDrug safety2013
Tyrosine kinase inhibitors: their on-target toxicities as potential indicators of efficacy.
Review in Drug safety, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 3 of them syntheses that pooled it.
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
83 citing papers in PubMed, 3 syntheses or guidelines pooled it, 145 citations in OpenAlex.
- Therapeutic Efficacy of Sorafenib in Patients with Hepatocellular Carcinoma Recurrence After Liver Transplantation: A Systematic Review and Meta-Analysis.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2021Pooled it
- Meta-analysis of the risks of hypertension and QTc prolongation in patients with advanced non-small cell lung cancer who were receiving vandetanib.European journal of clinical pharmacology · 2015Pooled it
- Incidence and relative risk of hepatic toxicity in patients treated with anti-angiogenic tyrosine kinase inhibitors for malignancy.British journal of clinical pharmacology · 2014Pooled it
- Clinical and metabolomic characterization of Brivanib-Induced hypertension in metastatic colorectal cancer.Cancer medicine · 2023Trial
- Dermatological Adverse Events Associated With Lapatinib Treatment in Dogs With Urothelial Carcinoma: A Retrospective Study.Veterinary dermatology · 2026Article
- Adverse side-effects of antifibrotic drugs in idiopathic pulmonary fibrosis-clarification of several points.Journal of thoracic disease · 2026Article
- Adverse side-effects of antifibrotic drugs and outcome of treatment in idiopathic pulmonary fibrosis.Journal of thoracic disease · 2025Article
- Cutaneous Adverse Effects of EGFR Therapy in Breast Cancer Treatment.Clinical and translational science · 2025Review
- An overview of strategies and challenges adopted to silence BCR-ABL gene by small interfering RNA.Nanomedicine (London, England) · 2025Review
- Modeling exposure-driven adverse events of EGFR TKIs in the treatment of patients with non-small cell lung cancer.Acta pharmacologica Sinica · 2025Article
- ExploringAdvanced pharmaceutical bulletin · 2025Article
- Reviewing the path to balance: mechanisms and management of hypertension associated with targeting vascular endothelium in cancer therapy.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Review
- Dasatinib-Induced Pulmonary Arterial Hypertension in Chronic Myeloid Leukaemia: A Case Report and Literature Review.Respirology case reports · 2025Article
- Effects of lenvatinib on glucose, cholesterol, triglycerides and estimated cardiovascular risk in patients with advanced thyroid cancer.Endocrine · 2025Article
- Drug Interaction of Dasatinib with Thymoquinone: A Pharmacokinetic Study in Rats.International journal of medical sciences · 2025Article
- Skin Toxicities Induced by Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and their Influence on Treatment Adjustments in Lung Cancer Patients.Acta dermato-venereologica · 2024Article
- The state of the art in secondary pharmacology and its impact on the safety of new medicines.Nature reviews. Drug discovery · 2024Review
- From Tyrosine Kinases to Tyrosine Phosphatases: New Therapeutic Targets in Cancers and Beyond.Pharmaceutics · 2024Review
- Prevalence and management of proteinuria associated with vascular endothelial growth factor receptor-targeted tyrosine kinase inhibitor treatment in advanced renal cell carcinoma, hepatocellular carcinoma, and thyroid cancer.International journal of urology : official journal of the Japanese Urological Association · 2024Review
- The Role of p90 Ribosomal S6 Kinase (RSK) in Tyrosine Kinase Inhibitor (TKI)-Induced Cardiotoxicity.Journal of cardiovascular translational research · 2024Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of certain forms of cancers, raising hopes for many patients with otherwise unresponsive tumours. While these agents are generally well tolerated, clinical experience with them has highlighted their unexpected association with serious toxic effects on various organs such as the heart, lungs, liver, kidneys, thyroid, skin, blood coagulation, gastrointestinal tract and nervous system. Many of these toxic effects result from downstream inhibition of vascular endothelial growth factor or epidermal growth factor signalling in cells of normal organs. Many of these undesirable effects such as hypertension, hypothyroidism, skin reactions and possibly proteinuria are on-target effects. Since tyrosine kinases are widely distributed with specific functional roles in different organs, this association is not too surprising. Various studies suggest that the development of these on-target effects indicates clinically desirable and effective inhibition of the corresponding ligand-mediated receptor linked with oncogenesis. This is reflected as improved efficacy in the subgroup of patients who develop these on-target adverse effects compared with those who do not. Inevitably, issues arise with respect to the regulatory assessment of efficacy and risk/benefit of the TKIs as well as the clinical approach to managing patients who develop these effects. Routine subgroup analysis of efficacy data from clinical trials (patients with and without on-target toxicity) may enable more effective clinical use of TKIs since (i) discontinuing or reducing the dose of the TKI has a negative impact if the tumour is TKI-responsive; and (ii) it is usually possible to manage these undesirable on-target effects with conventional clinical approaches. Prospective studies are needed to investigate this proposition further.
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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.