Tyrosine kinase inhibitor-induced hypertension—marker of anti-tumour treatment efficacy or cardiovascular risk factor?

Tyrosine kinase receptor inhibitors (TKIs) are a relatively new class of targeted anti-cancer agents with vascular endothelial growth factor signalling pathway–inhibiting properties. Hypertension is recognized as one of the most common adverse effects of this anti-angiogenic therapy and is the consequence of reduced production of vasodilatory nitric oxide and reduced prostacyclin production as well as increased production of vasoconstrictive endothelin-1. TKI-induced hypertension is dose dependent and it has been suggested as a marker of treatment effectiveness. In this issue, Saito et al. report the incidence of treatment-related hypertension in patients treated with lenvatinib, a newer TKI, for non-resectable hepatocellular carcinoma. The authors demonstrate that a subset of TKI-treated patients develop fluid retention 3 weeks after treatment initiation as a consequence of lower urinary sodium excretion and thus provides insights into the pathogenesis of blood pressure elevation in the second phase. These findings contribute to a better understanding of TKI-associated hypertension and help in choosing the most appropriate antihypertensive agents in this setting. Active control of hypertension may help more patients benefit from longer TKI therapy, possibly resulting in better cancer outcomes.