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Tyrosine Kinase Inhibitor-Induced Hypertension: Role of Hypertension as a Biomarker in Cancer Treatment

Author(s):

Cecilie Budolfsen, Julie Faber, Daniela Grimm*, Marcus Krüger, Johann Bauer, Markus Wehland, Manfred Infanger and Nils Erik Magnusson   Pages 1 - 17 ( 17 )

Abstract:


Cancer treatment is an area of continuous improvement. Therapy is becoming more targeted and the use of anti-angiogenic agents in multiple cancers, specifically tyrosine kinase inhibitors (TKIs), has demonstrated prolonged survival outcomes compared with previous drugs. Therefore, they have become a well-established part of the treatment.

Despite good results, there is a broad range of moderate to severe adverse effects associated with treatment. Hypertension (HTN) is one of the most frequent adverse effects and has been associated with favourable outcomes (in terms of cancer treatment) of TKI treatment.

High blood pressure is considered a class effect of TKI treatment, although the mechanisms have not been fully described. Three current hypotheses of TKI-associated HTN are highlighted in this narrative review. These include nitric oxide decrease, a change in endothelin-1 levels and capillary rarefaction.

Several studies have investigated HTN as a potential biomarker of TKI efficacy. HTN is easy to measure and adding this factor to prognostic models has been shown to improve specificity. HTN may become a potential biomarker in clinical practice involving treating advanced cancers. However, data are currently limited by the number of studies and knowledge of the mechanism of action.

Keywords:

Tyrosine kinase inhibitors, hypertension, biomarker, tyrosine kinase inhibitor-induced hypertension, cancer treatment, sorafenib, sunitinib, lenvatinib.

Affiliation:

Department of Biomedicine, Pharmacology, Aarhus University, Wilhelm Meyers Allé 4, 8000 Aarhus C, Department of Biomedicine, Pharmacology, Aarhus University, Wilhelm Meyers Allé 4, 8000 Aarhus C, Department of Biomedicine, Pharmacology, Aarhus University, Wilhelm Meyers Allé 4, 8000 Aarhus C, Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University, Leipziger Str. 44, 39120 Magdeburg, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University, Leipziger Str. 44, 39120 Magdeburg, Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University, Leipziger Str. 44, 39120 Magdeburg, Diabetes and Hormone Diseases - Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, Palle Juul-Jensens Boulevard 165, 8200 Aarhus N



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