Onco-hypertension: Overview of hypertension with anti-cancer agents

Abstract

Onco-hypertension is an emerging field investigating the relationship between hypertension and cancer. This paper details one part of this relationship—the effect of anti-cancer agents on blood pressure. We review the evidence linking targeted therapies, immunotherapy, traditional chemotherapies, and hormonal agents with hypertension. Proposed pathophysiological mechanisms vary by drug but include endothelial dysfunction, altered sodium homeostasis, and nephrotoxicity. Despite growing interest in the field, there is a paucity of data on the clinical significance of treatment related hypertension and the optimal management strategy. This should be a focus of future studies.

Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension—Mechanisms and Mitigation

“…However, it has been suggested that a decrease in downstream hsp70 (heat shock protein 70) may be associated along with decreased PI3K (phosphatidylinositol 3-kinase) signaling resulting in downstream depletion of NO production and reduced VEGF propagation with eventual vascular remodeling and endothelial cell dysfunction. 13,121,128,129…”

“…227 Navigating the complexity of decisions around antihypertensive treatment selection with consideration of drug pharmacokinetics and pharmacodynamics, with the appreciation of both potential side effects and individual patient comorbidities requires a multidisciplinary approach and supports a shift in our practice of CVD management in patients with cancer towards an individualized approach within the growing concept of oncohypertension. 11,13,211,222…”

“…Our current knowledge of VEGFi-induced hypertension largely stems from an established understanding of chemotherapy-induced hypertension which revolves around two major mechanisms: endothelial dysfunction and microvascular rarefaction. 8,13,19,45,[73][74][75][76] VEGF signaling pathway disruption/inhibition is a critical factor leading to endothelial dysfunction in numerous chemotherapies. Despite their established use, a complete understanding of the molecular processes driving VEGFi-induced hypertension and vascular toxicities remains unclear.…”

“…140,141 This difference may also be in part attributed to drug delivery method (intermittent intravenous infusion opposed to regular oral dosing). 13,133 Mechanism of PI3Ki-Induced Hypertension Although the pathophysiology behind PI3Ki-induced hypertension is not yet characterized, it is postulated that PI3K plays a role in the endothelial cell function, whereby inhibition results in endothelial dysfunction and vasoconstriction. 142 Furthermore, PI3K isoforms may help regulate blood pressure via type-1 angiotensinreceptor signaling which has led to exploration of the therapeutic antihypertensive utility of this pathway.…”

“…Oncohypertension takes a broader approach to the understanding and management of hypertension, whilst acknowledging the gaps in evidence and the complexity of integrated factors including comorbidities, the choice of anticancer treatments, the cancer type, and patient factors. [11][12][13] Recent developments in this area include a harmonized definition for hypertension in patients with cancer, which we will discuss here. We will furthermore reflect on blood pressure surveillance and management strategies for patients undergoing cancer therapies, including new models of care such as remote monitoring.…”