Cancer and Hypertension: Shared Mechanisms, Treatment Interactions, and Clinical Management

ABSTRACT

Cancer and hypertension (HTN) frequently coexist, and their relationship is increasingly recognized as a clinically relevant intersection between oncology and cardiovascular medicine. However, the extent to which this association reflects shared risk factors, common biological mechanisms, or treatment‐related effects remains incompletely understood. In this narrative review, we focus specifically on the cancer–HTN interface and summarize epidemiological evidence while considering the potential influence of age, obesity, metabolic syndrome, dietary patterns, and psychosocial factors. We further discuss overlapping mechanisms, including chronic inflammation, renin–angiotensin–aldosterone system activation, calcium signaling abnormalities, activation of the sympathetic nervous system, metabolic dysregulation, dysbiosis of the gut microbiota and genetic and epigenetic alterations. Particular attention is given to the bidirectional interactions between cancer therapies and HTN, as well as the heterogeneous evidence concerning potential associations between antihypertensive medications and cancer outcomes. We also summarize the clinical assessment and management of cancer therapy‐related HTN, including Common Terminology Criteria for Adverse Events grading, blood pressure monitoring, cardiovascular risk assessment, and current recommendations from the European Society of Hypertension (ESH) and American Heart Association. Emerging issues, including immune checkpoint inhibitor‐associated cardiovascular toxicity, the potential role of cardiac biomarkers such as troponin and natriuretic peptides, and the prognostic significance of treatment‐induced HTN across different tumor types, are also discussed. Overall, the available evidence supports an important clinical interplay between cancer and HTN but does not establish a uniform causal relationship. Future prospective studies integrating tumor biology, cardiovascular risk factors, treatment exposure, and longitudinal blood pressure (BP) assessment are needed to clarify these interactions and improve individualized cardio‐oncology care.

1. Introduction

Both economically developed and developing countries face cancer as a disease that imposes a tremendous social and economic burden. Epidemiological data show that in 2012, there were approximately 14.1 million new cancer cases and 8.2 million cancer‐related deaths globally [1]; by 2020, these numbers had risen to about 19.3 million new cases and 10 million deaths [2]. It is predicted that by 2070, the overall incidence of all cancers will double compared with 2020 [3], indicating that the burden of cancer has been increasing recently.

Hypertension (HTN) is one of the common comorbidities of cancer [4]. It is a cardiovascular condition characterized by persistently elevated blood pressure (BP). HTN affects approximately 30%–40% of adults worldwide [5]. The burden of HTN is substantial because it markedly increases the risk of cardiovascular morbidity and mortality. Mounting evidence indicates that HTN may increase the risk of cancer incidence [6, 7]. Conversely, cancer can also elevate the risk of developing HTN [8, 9, 10]. These findings suggest that the two diseases may share common risk factors and pathogenic mechanisms and may also interact through treatment‐related effects. Therefore, understanding the relationship between cancer and HTN is crucial for public health management, diagnosis, and treatment.

In this narrative review, we summarize the epidemiological evidence, shared risk factors and mechanisms underlying the cancer–HTN interface, as well as treatment‐related interactions and current approaches to clinical management.

2. Bidirectional Associations Between Cancer and Hypertension

Growing evidence indicates a close relationship between HTN and cancer, and their coexistence may be associated with poorer clinical outcomes. A follow‐up study of 577,799 adults revealed that in men, mean arterial pressure was positively correlated with the overall risk of cancer incidence (including oropharyngeal, colon, rectal, lung, bladder, kidney, malignant melanoma, and non‐melanoma skin cancers (NMSC)). In women, mean arterial pressure was not associated with overall cancer incidence but was positively associated with liver, pancreatic, cervical, and uterine cancers, malignant melanoma, and cancer mortality [7]. A meta‐analysis demonstrated a significant positive association between HTN and breast cancer risk, particularly among postmenopausal women with HTN [6]. Epidemiological studies show that hypertensive patients have a higher risk of renal cell carcinoma than normotensive patients. The observed association may be influenced by factors including smoking, obesity, and antihypertensive treatment [11, 12]. Meta‐analyses suggest a positive relationship between HTN and colorectal cancer, with a stronger association observed in men than in women [13]. A study of 246 patients with stage IB1 cervical cancer demonstrated that HTN was positively associated with local invasion in cervical cancer [14]. A study analyzing the link between BP and cancer risk indicated positive associations between HTN and kidney cancer, colorectal cancer, and breast cancer. Moreover, positive relationships were detected between HTN and the risk of esophageal adenocarcinoma, squamous cell carcinoma, liver cancer, and endometrial cancer. This meta‐analysis suggests that individuals with HTN may also be at higher risk for colorectal and breast cancer [15]. A follow‐up study of 27,332 Japanese individuals aged 40–79 over 18.5 years discovered that HTN was associated with higher all‐cause mortality, primarily due to esophageal, liver, and pancreatic cancers [16]. A retrospective observational analysis of mortality data among the U.S. adult population from 1999 to 2023 showed a continuous rise in cancer and HTN‐related mortality, particularly among men, non‐Hispanic Black Americans, and those in southern and rural areas [17]. As cancer survivors live longer, the prevalence of age‐related health issues, particularly cardiovascular diseases, has increased. In terms of mortality, HTN is the leading risk factor for non‐communicable diseases, accounting for 13.5% of premature deaths [9]. A retrospective analysis of a large cohort of 747,620 individuals with HTN between January 2005 and May 2022 found that HTN patients with a history of cancer had an elevated risk of composite cardiovascular disease events (myocardial infarction [MI], heart failure [HF], angina pectoris [AP], stroke, and atrial fibrillation [AF]), particularly those undergoing aggressive chemotherapy [18]. An analysis of deaths from specific cardiovascular diseases among American cancer patients from 1999 to 2019 revealed that across all cancer types, the proportion of cardiovascular deaths caused by ischemic heart disease showed a declining trend, while the proportion of deaths due to hypertensive diseases exhibited the largest increase [19]. Taken together, these epidemiological findings suggest that HTN was associated with a higher incidence of cancer, whereas patients with cancer had a higher prevalence of HTN. The associated malignancies include oropharyngeal, colon, rectal, lung, bladder, kidney, malignant melanoma, NMSC, liver, pancreatic, cervical, uterine, breast cancer, and renal cell carcinoma. However, owing to the limited epidemiological studies reviewed, regional and population‐specific variations were not examined.

Prospective cohort studies and meta‐analyses provide relatively stronger evidence for population‐level associations, whereas retrospective studies may be influenced by selection bias, reverse causality, confounding by indication, and incomplete adjustment for shared risk factors. Experimental studies, including cell‐based and serum‐transfer experiments, can provide important mechanistic insights but should not be interpreted as evidence of clinical causality. Importantly, the association is not consistent across all cancer types. Evidence for renal cell carcinoma and endometrial cancer is comparatively more consistent, whereas findings for several other malignancies remain heterogeneous. Therefore, the presence of a statistically significant association in an individual study should not be interpreted as evidence that HTN independently increases cancer risk. The strength of inference should instead depend on study design, adjustment for major confounders, consistency across populations, biological plausibility, and evidence from prospective or interventional studies. Accordingly, the available evidence suggests that cancer and HTN may be bidirectionally associated, and this bidirectional relationship may be attributable to shared risk factors, common pathogenic mechanisms, or adverse effects of therapeutic interventions. In the following sections, we discuss these potential mechanisms in detail to further elucidate the biological basis of the association between cancer and HTN.

3. Shared Risk Factors and Confounding in the Cancer–Hypertension Association

Cancer and HTN share several established risk factors, including advanced obesity, age, metabolic syndrome (MetS), diabetes, dyslipidemia, smoking, alcohol consumption, physical inactivity, psychosocial factors, and unfavorable dietary patterns [20, 21]. Because these factors independently influence both cancer and cardiovascular outcomes, they may contribute substantially to the observed epidemiological association between cancer and HTN.

Obesity represents an important shared determinant linking HTN and cancer. Epidemiological studies have consistently demonstrated that excess adiposity, particularly visceral obesity, increases the risk of HTN through multiple mechanisms, including sympathetic nervous system activation, renin–angiotensin–aldosterone system (RAAS) overactivation, renal sodium retention, endothelial dysfunction, oxidative stress, and chronic low‐grade inflammation [22, 23]. Obesity‐related adipose tissue dysfunction, characterized by increased secretion of pro‐inflammatory cytokines (e.g., TNF‐α and IL‐6), elevated leptin levels, and reduced adiponectin production, contributes to vascular impairment and metabolic abnormalities that promote BP elevation [24]. Importantly, obesity should not be considered merely as a confounding factor but also as a potential mediator, because the same biological alterations may influence tumor initiation and progression. Excess adiposity promotes carcinogenesis through overlapping metabolic and inflammatory pathways, including insulin resistance, hyperinsulinemia, activation of insulin/IGF‐1 signaling, oxidative stress, chronic inflammation, and altered sex hormone metabolism [25, 26]. Adipose tissue‐derived inflammatory mediators and adipokines can facilitate tumor growth, angiogenesis, and immune dysregulation, thereby creating a tumor‐supportive microenvironment [27]. In addition, obesity‐related RAAS activation may provide a mechanistic link between HTN and cancer by promoting vascular dysfunction, inflammation, and angiogenic signaling [28, 29, 30, 31]. Therefore, incomplete adjustment for obesity and related metabolic abnormalities may partially explain the association observed between HTN and cancer in epidemiological studies. Future investigations should consider obesity, metabolic syndrome, and body composition as key factors when evaluating whether HTN independently contributes to cancer risk.

Age is an important shared determinant and potential confounder in the association between HTN and cancer. Both HTN prevalence and cancer incidence increase substantially with advancing age, suggesting that their epidemiological coexistence may be partly attributable to aging [32, 33, 34]. As individuals age, progressive vascular remodeling, arterial stiffening, and endothelial dysfunction contribute to increased vascular resistance and sustained BP elevation, thereby promoting the development of HTN [35]. In parallel, the accumulation of genomic damage, epigenetic alterations, mitochondrial dysfunction, telomere attrition, and impaired tissue homeostasis increases cellular vulnerability to malignant transformation [36, 37]. Beyond these condition‐specific pathways, aging‐related immunosenescence and inflammaging may provide a biological link between HTN and cancer. Age‐associated immune dysregulation may contribute to vascular injury and impaired endothelial homeostasis, while persistent low‐grade inflammation and declining immune surveillance may facilitate a tumor‐supportive microenvironment and cancer progression [38]. Importantly, the association between HTN and cancer may depend on the age at which antihypertensive treatment is initiated. A population‐based study found that the association between treated HTN and cancer risk varied significantly according to age at treatment initiation, highlighting the potential influence of age on the observed association between the two conditions [38]. Collectively, these findings suggest that the increased coexistence of HTN and cancer among older individuals may reflect, at least in part, the shared consequences of biological aging rather than a direct causal effect of HTN on cancer. Therefore, age should be appropriately accounted for in epidemiological analyses of the HTN–cancer association to minimize residual confounding and avoid overestimating an independent association between the two conditions.

MetS represents another important shared metabolic determinant linking HTN and cancer. Characterized by a cluster of central obesity, insulin resistance, dyslipidemia, and elevated BP, MetS promotes HTN through sympathetic overactivity, activation of RAAS, renal sodium retention, endothelial dysfunction, oxidative stress, and chronic low‐grade inflammation [39, 40]. At the same time, the metabolic abnormalities underlying MetS may promote carcinogenesis through hyperinsulinemia, insulin/insulin‐like growth factor‐1 signaling, chronic inflammation, oxidative stress, and adipokine dysregulation. A systematic review and meta‐analysis of 43 studies found that MetS was associated with increased risks of several malignancies, including colorectal, liver, pancreatic, endometrial, and postmenopausal breast cancers, although the magnitude of associations varied according to sex, cancer site, and population [41]. More recent umbrella‐review evidence likewise suggests that MetS is associated with a modestly increased risk of obesity‐related cancers, particularly colorectal cancer, but also indicates substantial heterogeneity and differences in the strength of evidence across cancer types [42]. Therefore, MetS may contribute to the coexistence of HTN and cancer through both shared metabolic risk factors and overlapping biological pathways, while incomplete adjustment for its individual components may introduce residual confounding in observational studies evaluating the cancer–HTN association.

Dietary patterns represent important modifiable determinants shared by HTN and cancer. Diets characterized by high sodium intake, excessive consumption of processed foods, refined carbohydrates, and saturated fats, together with inadequate intake of fruits, vegetables, and whole grains, have been associated with increased HTN risk through mechanisms involving sodium retention, endothelial dysfunction, oxidative stress, and chronic inflammation [43, 44]. The same unhealthy dietary patterns may promote carcinogenesis by inducing metabolic disorders, insulin resistance, oxidative stress, and inflammatory responses, thereby facilitating tumor initiation and progression [45]. Conversely, adherence to healthy dietary patterns, such as the Dietary Approaches to Stop Hypertension (DASH) diet, has been associated with reduced risks of both cardiovascular disease and cancer, likely through improvements in metabolic homeostasis and inflammatory regulation [46, 47]. Therefore, dietary factors may serve as shared biological pathways linking HTN and cancer, and inadequate adjustment for dietary patterns may contribute to residual confounding in epidemiological studies evaluating the association between these two diseases.

Furthermore, psychosocial factors are risk factors for the pathogenesis of various diseases. Studies have shown that the prevalence of HTN is higher among individuals with depression than those with other psychiatric disorders [48] and depressive and anxiety symptoms are commonly observed in hypertensive patients [49]. These emotional changes contribute to BP dysregulation and increased vascular risk [50, 51]. Additionally, a follow‐up survey demonstrated that depression and anxiety symptoms accompanying HTN were related to an elevated risk of developing lung, oral, prostate, and skin cancers, as well as a higher risk of cancer‐specific mortality from lung, bladder, breast, colorectal, hematopoietic system, renal, and prostate cancers [52]. Socioeconomic status may also introduce residual confounding. Education, income, healthcare access, health literacy, cancer screening, medication adherence, and lifestyle behaviors may influence both the detection of cancer and the diagnosis and control of HTN. Differences in screening and healthcare utilization may therefore affect the apparent strength of the cancer–HTN association.

Taken together, shared risk factors provide a plausible explanation for the epidemiological overlap between HTN and cancer. However, because many of these factors simultaneously influence cardiovascular health and tumor biology, incomplete adjustment for age, obesity, smoking, metabolic abnormalities, and socioeconomic status may overestimate the strength of the HTN–cancer association. Future studies using longitudinal designs, detailed metabolic phenotyping, and appropriate adjustment for shared determinants are required to clarify whether HTN and cancer share common risk factors for disease development.

4. Shared Biological Mechanisms Linking Cancer and Hypertension

Cancer and HTN are both complex and heterogeneous diseases involving multiple interacting biological processes rather than a single pathogenic pathway. Cancer development involves genetic and epigenetic alterations, metabolic reprogramming, and remodeling of the tumor microenvironment, among other processes (Table S1 and Figure S1). In contrast, HTN arises from the interaction of multiple factors, including vascular dysfunction, renal abnormalities, and inflammation, among other processes (Table S2 and Figure S2).

Although their individual pathogenic processes differ, increasing evidence suggests that cancer and HTN may converge on several interconnected biological pathways. These shared processes include chronic inflammation, RAAS activation, endothelial dysfunction, oxidative stress, metabolic dysregulation, abnormal calcium signaling, and angiogenic imbalance. Importantly, the strength of evidence supporting these mechanisms differs substantially.

Evidence from human epidemiological studies provides the strongest support for an association between specific cancer types and HTN, whereas experimental studies primarily provide mechanistic plausibility. In vitro and animal studies should therefore not be interpreted as equivalent to prospective clinical evidence. For example, experimental findings demonstrating that circulating factors from hypertensive patients alter endothelial or tumor‐cell behavior may support biological plausibility, but they cannot establish that HTN independently causes cancer in humans.

Accordingly, the mechanisms discussed below should be viewed as interconnected biological hypotheses rather than as independently established causal pathways. Several mechanisms may also represent consequences of cancer or its treatment rather than causes of cancer development. This bidirectionality is particularly important because systemic inflammation, metabolic abnormalities, renal dysfunction, and endothelial injury can occur both before and after cancer diagnosis.

The convergence of these pathways provides a biologically plausible framework through which cancer and HTN may influence one another. Future studies integrating longitudinal BP measurements with molecular, metabolic, and tumor‐specific biomarkers will be required to determine which pathways represent causal drivers and which reflect downstream consequences of either disease or its treatment.

4.1. Inflammation

The tumor microenvironment, which includes inflammatory cells and cytokines, contributes to tumor initiation and metastasis. Similarly, HTN is a chronic inflammatory condition, and suppressing inflammation can improve HTN, indicating that inflammation is a common pathological mechanism for both diseases [10]. Consistent with these findings, clinical studies have shown that an elevated red blood cell distribution width‐to‐albumin ratio (RAR), reflecting systemic inflammation and nutritional imbalance, is associated with increased mortality risk among hypertensive populations [53]. As inflammation constitutes a common pathogenic mechanism in cancer and HTN, suppressing inflammatory responses is essential for the treatment of both conditions.

4.2. Activation of RAAS

Research indicates that the RAAS is activated in cancers such as renal cell carcinoma, gastric cancer, and cervical cancer, suggesting a close relationship between RAAS activation and tumor progression. RAAS is also activated in HTN [54]. In both cancer and HTN, the RAAS effector Ang II binds to AT₁R and AT₂R, activating downstream signaling pathways such as MAPK, PI3K/AKT, NF‐κB, and JAK/STAT, and increasing the expression of VEGF, TGF‐β1, EGFR, and fibronectin, ultimately leading to cell proliferation, angiogenesis, and fibrosis [54]. Evidence indicates that localized RAAS activation in adipocytes of obese patients, via Ang II‐AT₁R axis stimulation, triggers secretion of pro‐inflammatory cytokines, adipokines, and growth factors. These bioactive molecules subsequently activate PI3K/AKT and NF‐κB signaling cascades, enhancing breast cancer cell viability, proliferation, and neovascularization while upregulating oncogenic gene and protein expression [31]. This molecular mechanism underlies the pathophysiological crosstalk among RAAS dysregulation, obesity, and breast cancer progression. These studies further demonstrate that the pathogenic risk factors for both conditions are interconnected through complex biological networks. This underscores the necessity of comprehensive strategies targeting lifestyle behaviors, exercise habits, and clinical treatments to prevent and control both cancer and HTN.

4.3. Dysregulation of Calcium Ion (Ca²⁺) Homeostasis

Ca²⁺ is a ubiquitous multifunctional signaling molecule that controls numerous cellular processes, and Ca²⁺ homeostasis is considered a key driver in the development and progression of malignant diseases [55]. In HTN, Ang II activates the PLC/IP3 signaling pathway to increase free Ca²⁺ levels in VSMCs, leading to vascular smooth muscle contraction and ultimately elevated BP [56, 57]. In cancer, Ca²⁺ signaling is involved in cancer cell proliferation, invasion, death, and immune response, while also suppressing the expression of tumor suppressors, thereby contributing to cancer development [55, 56, 57, 58]. Clinical studies show that Ca²⁺/cAMP signaling can promote inflammation, thereby increasing the risk of HTN and cancer development [59]. Collectively, these findings indicate that dysregulated Ca²⁺ signaling contributes to the pathogenesis of both HTN and cancer. Consequently, targeting Ca²⁺ signaling disturbances represents a viable therapeutic strategy for the management of both conditions.

4.4. Activation of the Sympathetic Nervous System

As mentioned above, sympathetic activation and stimulation of β‐adrenergic receptors can contribute to the development of HTN. In addition, sympathetic signaling exerts pro‐tumor effects in prostate cancer, breast cancer, and melanoma. On the other hand, parasympathetic/vagus nerve activation facilitates tumor progression in prostate, gastric, and colorectal cancers. These neural effects can be explained by alterations in cancer cell behaviors (e.g., proliferation, migration, apoptosis, and metastasis), angiogenesis, inflammation, cellular immune responses, and EMT [60, 61]. Taken together, these findings indicate that sympathetic nervous system activation promotes the development of both cancer and HTN; thus, it represents a potential therapeutic target for both diseases.

4.5. Metabolic Dysregulation

As previously discussed, the development and progression of cancer involve alterations in metabolic pathways such as glycolysis, amino acid metabolism, and lipid metabolism. Similarly, HTN is characterized by metabolic dysregulation. Compared to healthy individuals, hypertensive patients exhibit elevated serum levels of arginine and homocysteine, along with decreased levels of methionine and alanine [62]. The lactate/pyruvate ratio is also increased [62]. Numerous studies support the association between disrupted arginine metabolism and HTN. For instance, impaired transport of L‐arginine into endothelial cells and inhibition of NO synthesis by high concentrations of arginine have been observed [62]. Clinical studies indicate enhanced conversion of methionine to homocysteine, wherein cysteine reduces NO bioavailability, thereby promoting elevated BP [62]. In HTN, depletion of alanine stimulates insulin release, which subsequently affects BP; animal studies demonstrate that diminished action of alanine on cardiac sympathetic norepinephrine release contributes to HTN [62].

Research has shown that serum levels of zinc‐alpha 2‐glycoprotein (ZAG) are reduced in hypertensive patients compared to healthy controls. Decreased ZAG expression inhibits CPT1 activity, leading to reprogramming of renal lipid metabolism. This results in fatty acid accumulation, increased Na⁺/H⁺ exchanger (NHE) activity, and reduced urinary Na⁺ excretion, ultimately contributing to the development of HTN [63]. Another study identified potential novel biomarkers for HTN‐related disorders, including higher levels of acetate, formate, and glycerol, and lower levels of glutamine, glycine, and sarcosine [64]. Impaired glucose oxidative metabolism and enhanced glycolysis represent characteristic metabolic patterns in the development of pulmonary arterial HTN, primarily by promoting proliferation of pulmonary arterial smooth muscle cells and vascular cells, as well as stimulating neointimal formation, thereby exacerbating pulmonary vascular lesions [65]. Ang II induces a metabolic shift from OXPHOS to aerobic glycolysis in cardiac fibroblasts (CFs), which promotes myocardial remodeling in HTN [66]. The sirtuin (SIRT) family influences macrophage immune function and inflammatory responses by regulating glucose, lipid, and amino acid metabolism. Additionally, SIRTs modulate glycolytic processes in macrophages, affecting their energy supply and generating metabolites that further shape immune and inflammatory responses, thereby facilitating the onset and progression of HTN [67]. Thus, metabolic dysregulation may serve as a common pathogenic mechanism underlying both cancer and HTN. In recent years, metabolic disorders have garnered increasing attention from researchers, clinicians, and patients. However, the contribution of metabolic dysfunction to the development of HTN and cancer remains incompletely understood. Therefore, continued vigilance regarding diseases arising from metabolic disturbances remains essential.

4.6. Dysbiosis of the Gut Microbiota

The human gut is one of the most complex networks in the human body, hosting trillions of microorganisms, such as bacteria, archaea, fungi, protists, and viruses [68]. Under normal circumstances, the gut microbiota maintains a certain balance. Alterations in the intestinal environment can induce abnormal immune responses; gut microorganisms can induce abnormal immune responses in colorectal tissues, thereby contributing to tumor‐promoting immune microenvironments, weakening the intestinal epithelial barrier, and generating oncogenic toxins that have an effect on intestinal epithelial cells, promoting abnormal cellular proliferation. Additionally, these toxins generate carcinogenic metabolites, leading to host cell DNA damage and inducing mutagenic ROS and other free radicals. These mechanisms collectively contribute to colorectal tumorigenesis [69]. Similarly, inflammation induced by enterotoxigenic Bacteroides fragilis (ETBF) promotes cancer pathogenesis through STAT3‐ and Th17‐dependent pathways, while the inflammatory state increases the ROS generation, which triggers DNA damage and facilitates tumor progression. Gut microbiota can also promote the pathogenesis of liver cancer by inhibiting the function of hepatic immune cells [70]. Gut microbiota dysbiosis can also contribute to gastric, pancreatic, breast, and prostate cancers [71], highlighting the important role of the gut microbiota in the initiation and progression of cancer. Animal studies have shown alterations in gut microbiota in hypertensive animal models [72], such as a lower abundance of SCFA‐producing bacteria and Bacteroidetes and higher abundance of Proteobacteria and Cyanobacteria compared with control animals [73]. Several human cross‐sectional studies have illustrated that HTN is related to lower gut microbiota alpha‐diversity [73, 74]. In addition, higher abundances of Gram‐negative microbiota, including Klebsiella, Parabacteroides, Desulfovibrio, and Prevotella, were associated with higher BP. The microbiota contributes to elevated BP by activating inflammatory responses, stimulating the sympathetic nervous system, altering BP‐related metabolic profiles, and interacting with HTN susceptibility genes [73, 74]. The above evidence suggests that gut microbiota dysbiosis is a common pathogenic mechanism in both cancer and HTN, and targeting this imbalance through therapeutic interventions may improve both conditions. In recent years, the gut microbiome has become a rapidly expanding area of investigation. While various probiotic interventions, including lactic acid bacteria preparations, have entered clinical use, further development of targeted microbiota modulation strategies is anticipated to provide novel therapeutic avenues for HTN and malignancy.

4.7. Genetic and Epigenetic Alterations

As mentioned earlier, genetic alterations and epigenetic dysregulation are mechanisms underlying both cancer and HTN. It is hypothesized that a single gene may regulate both cancer and HTN, and its dysregulation could simultaneously contribute to the development of both conditions. A retrospective cohort study utilizing data from the UK Biobank evaluated the influence of the insulin‐like growth factor 1 (IGF1) variant rs2016347 on the risk of breast cancer, non‐breast cancers, and cardiovascular diseases among women with a history of hypertensive disorders of pregnancy (HDP). The results demonstrated that, compared to those with the guanine/guanine (G/G) genotype, women who experienced HDP and carried the thymine (T) allele of rs2016347 had a 41% reduced risk of non‐breast cancers and a 2.08 mmHg reduction in systolic BP. This suggests that variations in the IGF1 genotype may influence both cardiovascular and cancer risks in women with a history of HDP, thereby supporting the aforementioned hypothesis [75]. As a key component of the RAAS, angiotensin‐converting enzyme (ACE) was investigated through an analysis of the ACE I/D polymorphism genotype in a South American population and its association with major diseases and related conditions. The findings revealed that carriers of the DD genotype faced a higher risk of systemic HTN, and women with the DD genotype were more susceptible to endometrial cancer. This indicates that the same ACE genotype alteration may contribute to the development of both HTN and cancer [76]. Genotyping of G protein‐coupled receptor kinase 4 (GRK4) SNPs in breast cancer cDNA arrays displayed that the prevalence of individuals carrying two HTN‐related SNPs, A142V or R65L, is threefold higher in breast cancer patients than in healthy individuals [77]. Therefore, cancer and HTN can occur simultaneously because they share the same pathogenic mechanisms and risk factors. Genetic alterations may arise from environmental exposures, such as ultraviolet (UV) and ionizing radiation, as well as from inherited genetic susceptibility. Therefore, minimizing environmental and occupational radiation exposure is warranted. Individuals with a family history of hereditary susceptibility should undergo early genetic screening to reduce the risk of developing both cancer and HTN.

4.8. Reciprocal Pathogenic Mechanisms of Cancer and Hypertension

Studies have shown that HTN increases the risk of renal cancer in both genders, endometrial cancer in women, and prostate cancer in men [78]. Compared to non‐hypertensive individuals, among 1994 (25%) hypertensive patients who underwent regular cancer screening prior to cancer diagnosis, hypertensive patients receiving regular screening were more likely to develop metastatic cancer, whereas this association was reversed in those without regular screening. Treated hypertensive patients showed a significant increase in the probability of thyroid metastasis compared to the control group [79]. This suggests that HTN may be associated with malignancy risk, potentially by promoting the growth or dissemination of malignant cells, leading to cancer development. Alternatively, hormones secreted during the progression of HTN—including vasoactive hormones such as Ang II, catecholamines, and vasopressin, as well as metabolic hormones like insulin, mineralocorticoids, and glucocorticoids—may exert mitogenic effects [80], thereby contributing to carcinogenesis. To further investigate whether HTN can promote cancer, researchers treated various cancer cells with serum from hypertensive patients. The results demonstrated that endothelial cells treated with hypertensive serum enhanced the adhesion and invasiveness of ovarian (SKOV‐3), colorectal (SW480), breast (MCF‐7), and lung (A549) cancer cells. Additionally, expression of several pro‐oncogenic genes, such as CXCL8, TPA, and VEGF, was upregulated, further supporting the role of HTN in promoting cancer [81]. Furthermore, cancer can induce HTN. Cancers, including lung, pancreatic, thyroid, and ovarian cancers, as well as neuroblastoma, can produce adrenocorticotropic hormone (ACTH), which leads to elevated BP [82]. Clinical studies have also detected increased levels of ACTH in the blood of cancer patients [83]. Emerging evidence supports a reciprocal relationship between HTN and cancer, potentially mediated by shared pathogenic mechanisms such as inflammation, RAAS activation, metabolic dysfunction, and gut microbiome perturbation. However, the exact mechanisms linking these two conditions remain incompletely understood and require further investigation (Figure 1).

FIGURE 1.

Bidirectional associations between cancer and hypertension. The figure was created by the authors using Figdraw (https://www.figdraw.com). No AI‐assisted image generation tools were used in the preparation of this figure.

5. Treatment Methods

5.1. Anticancer Therapy–Associated Hypertension

Anticancer therapy can cause various forms of cardiovascular toxicity, with treatment‐related HTN being a clinically important component of the cancer–HTN interface. However, the risk of HTN is not uniform across anticancer treatments and depends on the drug class, treatment regimen, tumor type, treatment duration, and baseline cardiovascular risk. Among currently used anticancer therapies, inhibition of the VEGF/VEGFR pathway has the most consistent evidence for a direct association with HTN, whereas the evidence for other treatment classes is more heterogeneous [8, 10]. VEGF pathway inhibition provides the clearest example of treatment‐related HTN. Bevacizumab, for example, may induce vascular rarefaction and reduce the production of the vasodilator nitric oxide (NO), thereby increasing vascular resistance and BP [84]. Similarly, vandetanib as a VEGFR/EGFR inhibitor has been associated with an increased incidence of HTN, although most cases are Grade I or II. The incidence and severity of HTN vary according to tumor type and treatment duration, with patients with medullary thyroid carcinoma (MTC) showing a particularly high incidence of all‐grade HTN [85]. The proposed mechanisms of vandetanib‐associated HTN include reduced microvessel density, endothelial dysfunction resulting from reduced NO production and increased oxidative stress, and alterations in neurohormonal signaling or RAAS [86, 87]. These findings are consistent with the broader biological effects of VEGF inhibition, in which impaired endothelial vasodilation and microvascular remodeling contribute to BP elevation. Additionally, the combination of olaparib (a PARP inhibitor) and cediranib may elevate the risk of HTN in cancer patients [88]. In prostate cancer, several treatment modalities, including corticosteroids, antiandrogens, immunotherapy, and radiotherapy, may increase BP or worsen pre‐existing HTN, highlighting the importance of cardiovascular risk assessment during treatment [89, 90]. Adjuvant therapies such as erythropoietin, nonsteroidal anti‐inflammatory drugs (NSAIDs), and corticosteroids may also contribute to BP elevation [91]. Radiotherapy for cancer can also cause HTN [8]. However, compared with VEGF/VEGFR‐targeted therapy, the evidence for these treatments is more heterogeneous, and their effects on BP may be mediated by multiple systemic and treatment‐specific mechanisms.

Cancer‐related procedures and local therapies may also affect BP regulation. Human studies suggest that tumor resection and radiotherapy can be associated with BP instability, non‐sustained HTN, orthostatic intolerance, and tachycardia, potentially reflecting disruption of baroreceptor‐mediated cardiovascular regulation [92]. These observations further indicate that BP abnormalities in patients with cancer cannot always be attributed to a single pharmacological mechanism and may arise from interactions among anticancer treatment, autonomic regulation, vascular function, and pre‐existing cardiovascular disease.

Importantly, treatment‐induced HTN may have a complex relationship with anticancer efficacy. In patients with metastatic renal cell carcinoma receiving the VEGF inhibitor sunitinib, the development of HTN has been associated with a more favorable prognosis, suggesting that BP elevation may reflect pharmacodynamic inhibition of the VEGF pathway in some treatment settings [93]. These findings suggest that treatment‐induced HTN associated with certain antineoplastic agents may be unavoidable, necessitating concomitant antihypertensive management. Nevertheless, this observation should not be interpreted as evidence that uncontrolled HTN is beneficial. Rather, it raises the possibility that treatment‐induced BP elevation may function as a marker of drug exposure or biological response in selected patients.

The relationship between immune checkpoint inhibitors (ICIs) and HTN is more complex. Unlike VEGF/VEGFR inhibitors, for which HTN is a well‐established adverse effect, current evidence does not consistently demonstrate that ICI monotherapy substantially increases the risk of HTN. A meta‐analysis of randomized trials found no significant increase in short‐term HTN following ICI initiation [94]. Nevertheless, ICIs can cause clinically important cardiovascular immune‐related adverse events, including myocarditis, arrhythmias, and other forms of cardiovascular toxicity. Therefore, new‐onset HTN during ICI treatment should be interpreted in the broader context of cardiovascular risk and concomitant anticancer therapy rather than being automatically attributed to immune activation. Importantly, the risk of HTN may increase substantially when ICIs are combined with anti‐angiogenic or tyrosine kinase inhibitors. Recent meta‐analytic evidence suggests that ICI–TKI combinations are associated with a substantially higher incidence of treatment‐related HTN than control therapy [95]. This finding is clinically relevant because combination regimens are increasingly used across multiple tumor types. In such patients, VEGF/VEGFR pathway inhibition may represent the dominant mechanism underlying BP elevation, while immune‐mediated cardiovascular toxicity represents an additional consideration.

Overall, the available evidence supports a hierarchy among anticancer treatment‐related effects on BP. The association between VEGF/VEGFR pathway inhibition and HTN is relatively well established and is supported by consistent clinical and mechanistic evidence [10, 84, 85, 86, 87]. In contrast, HTN associated with PARP inhibitors, hormonal therapies, radiotherapy, and supportive treatments is more heterogeneous and may depend substantially on treatment combinations and patient characteristics [8, 88, 89, 90, 91, 92]. Taken together, treatment‐related HTN should be considered a dynamic and treatment‐specific cardiovascular toxicity rather than a uniform adverse event across anticancer therapies. Baseline cardiovascular risk assessment, regular BP monitoring, early initiation of antihypertensive therapy when indicated, and individualized decisions regarding anticancer treatment interruption are therefore essential components of cardio‐oncology care (Figure 1).

5.2. Antihypertensive Medications and Cancer Risk

The potential relationship between antihypertensive medications and cancer risk remains controversial. Importantly, the available evidence does not indicate a consistent increase in overall cancer incidence across the major antihypertensive drug classes. A meta‐analysis of five commonly used antihypertensive drug classes found no significant effect on overall cancer incidence compared with untreated or control groups [96]. However, such analyses are limited by the use of drug‐class rather than individual‐drug comparisons and by the evaluation of overall cancer incidence rather than tumor‐specific outcomes. Consequently, the absence of an overall association does not exclude possible associations between individual antihypertensive agents and specific malignancies.

Observational evidence has suggested that antihypertensive treatment may be associated with selected tumor types. For example, use of antihypertensive medications has been associated with an increased risk of renal cell cancer but not bladder cancer [97]. In contrast, a systematic review and meta‐analysis found no significant association between ACE inhibitors (ACEIs), β‐blockers, calcium channel blockers (CCBs), or diuretics and colorectal cancer risk [98]. These findings illustrate an important feature of the literature: associations may differ substantially according to cancer site, and results observed for one malignancy should not necessarily be generalized to all cancers.

Evidence concerning ACEIs and angiotensin receptor blockers (ARBs) is similarly inconsistent. Some studies have reported a slightly higher incidence of malignant tumors among patients receiving ACEIs, whereas other studies have suggested a potential protective effect; however, the available evidence is insufficient to establish a causal relationship [99]. ACEIs have also been associated with an increased risk of lung cancer, while ARBs have been reported to show a dose‐dependent association with lung cancer and a modest increase in new cancer diagnoses, corresponding to an absolute risk increase of approximately 1.2% over four years [100]. Conversely, ARB use has been associated with a lower risk of colorectal cancer in some Asian populations, although these findings require confirmation in more diverse populations [98]. Other studies have found no increased overall cancer risk among patients with a history of ARB use and have even suggested a possible reduction in lung cancer incidence [101]. Taken together, these findings do not support a uniform carcinogenic or protective effect of RAAS blockade across different cancer types.

The evidence concerning β‐blockers is also heterogeneous. Observational database studies have reported an increased incidence of head and neck cancer and melanoma among β‐blocker users [102, 103]. In contrast, observational studies in patients with colorectal cancer have associated β‐blocker use with improved short‐ and long‐term survival, particularly among patients who did not undergo surgery [104, 105]. These apparently divergent findings may reflect differences in tumor biology, cancer stage, treatment setting, and patient characteristics rather than a simple class‐wide effect of β‐blockade. In addition, differences among individual β‐blockers, including receptor selectivity, dose, and duration of treatment, may further contribute to heterogeneity.

Similar inconsistencies have been reported for diuretics. Diuretic use has been associated with an increased risk of kidney cancer in a dose‐dependent manner [12], as well as with papillary renal cell carcinoma (pRCC) [106] and NMSC [107]. Long‐term use of thiazides has been associated with an elevated risk of melanoma and squamous cell carcinoma [100]. A potential biological explanation is that some diuretics may undergo conversion into mutagenic nitroso derivatives in the stomach [108]. Nevertheless, these observations are primarily derived from observational studies and therefore cannot establish whether the medication itself, cumulative exposure, the underlying indication for treatment, or other patient characteristics account for the observed associations.

CCBs provide perhaps the clearest example of apparently contradictory findings. Case–control studies have reported associations between CCB use and renal cancer [109], pRCC [80], lung cancer [110], skin cancer [103], prostate cancer [111], as well as breast ductal and lobular carcinomas [112]. One proposed mechanism is that CCBs may interfere with programmed cell death in response to DNA damage, thereby potentially facilitating tumorigenesis. However, other studies have found no association between CCB use and breast cancer risk [100], while CCB use among patients with HTN has been associated with a reduced incidence of gastric cancer [113]. A potential mechanism for the latter observation is the inhibition of programmed death‐ligand 1 (PD‐L1) transcription and expression by CCBs, which may suppress tumor growth [114].

The apparently conflicting associations observed for CCBs and other antihypertensive classes should therefore not be interpreted as evidence that these medications are simultaneously and universally carcinogenic and protective. Several factors may account for the heterogeneity. First, most positive associations are derived from observational studies, which are vulnerable to confounding by indication and residual confounding. Patients receiving different antihypertensive drugs may differ systematically in age, comorbidities, renal function, cardiovascular risk, healthcare utilization, and other characteristics that also influence cancer risk. Second, cancer is not a single disease; differences in tissue origin, molecular subtype, tumor biology, and latency may result in drug‐specific effects that are detectable for one malignancy but absent for another. Third, cumulative exposure and treatment duration may be important, particularly for cancers with long latency periods. Finally, differences in study populations, exposure definitions, cancer ascertainment, and statistical adjustment may contribute to inconsistent findings.

Therefore, the current evidence should be interpreted according to both the strength of the underlying study design and the specificity of the reported association. Associations derived from observational studies are useful for generating hypotheses concerning potential drug–cancer relationships but should not be considered equivalent to evidence of causality. Conversely, the absence of an association with overall cancer incidence does not necessarily exclude a potential effect on a specific tumor type. Importantly, the existing evidence does not provide a sufficient basis for avoiding otherwise indicated antihypertensive treatment solely because of a potential cancer risk. Antihypertensive therapy should primarily be selected according to established cardiovascular indications, patient characteristics, renal function, treatment tolerance, and the overall clinical context. Further studies with detailed assessment of individual drugs, cumulative exposure, treatment duration, cancer subtype, and major confounding factors are required to determine whether the observed associations represent true pharmacological effects (Figure 1).

6. Clinical Diagnosis and Treatment

Management of HTN in patients with cancer requires integration of conventional cardiovascular risk assessment with cancer‐specific treatment considerations. Although BP targets and antihypertensive treatment principles remain broadly consistent with general HTN guidelines, cancer patients require additional consideration of the timing, mechanism, severity, and reversibility of treatment‐related BP elevation.

Treatment‐related HTN is graded according to the Common Terminology Criteria for Adverse Events (CTCAE) (Table 1) [115, 116]. The 2023 ESH Guidelines for the management of arterial HTN and the 2025 American Heart Association/American College of Cardiology (AHA/ACC) Guideline provide evidence‐based recommendations for the management of anticancer therapy‐induced HTN, including the selection of appropriate antihypertensive agents [115, 116]. These recommendations provide clinicians with a framework for selecting antihypertensive treatment according to the individual clinical context. In the prevention and treatment of cancer‐associated HTN, priority should be given to prophylactic measures, encompassing education for patients undergoing radiotherapy and chemotherapy, as well as close surveillance of blood pressure variations to facilitate the early identification and management of hypertensive complications [115, 117]. Second, when cancer‐related HTN occurs, treatment should be carried out in accordance with the 2023 ESH Guidelines for the management of arterial HTN [115, 117] (Boxes 1 and 2). Finally, when cancer patients experience a hypertensive crisis during their treatment (such as acute heart failure), the causative anticancer therapy may need to be temporarily interrupted, and appropriate antihypertensive treatment and emergency measures should be taken [118].

TABLE 1.

Common terminology criteria for adverse events (CTCAE) and grades of HTN.

Grade	Blood pressure
Grade 1	Systolic BP 120–139 mmHg or diastolic BP 80–89 mmHg
Grade 2	Adult: Systolic BP 140–159 mmHg or diastolic BP 90–99 mmHg; recurrent or persistent; Pediatric and adolescent: Recurrent or persistent (≥ 24 h) BP >ULN; monotherapy indicated; systolic and/or diastolic BP between the 95th percentile and 5 mmHg above the 99th percentile; Adolescent: Systolic between 130 and 139 or diastolic between 80 and 89 even if < 95th percentile
Grade 3	Adult: Systolic BP 160–179 mmHg or diastolic BP 100–109 mmHg persisting over 1 h; SBP > 140 mmHg plus either an increase in SBP of > 20 mmHg or an increase in MAP of > 15 mmHg from baseline; Pediatric and adolescent: Systolic and/or diastolic > 5 mmHg above the 99th percentile
Grade 4	Adult and Pediatric: SBP ≥ 180 or DBP ≥ 110 mmHg persisting over 1 h; BP associated with acute HTN—mediated organ damage; life—threatening consequences (e.g., malignant HTN, transient or permanent neurologic deficit, hypertensive crisis); urgent intervention indicated.
Grade 5	Death

BOX 1. Key points for treating HTN caused by cancer treatment.

• ACEIs or ARBs are the first‐line antihypertensive drugs recommended for BP management in patients with cancer.

• Dihydropyridine CCBs are recommended as second‐line antihypertensive drugs for patients with cancer whose BP remains uncontrolled.

• Combination therapy with ACEI or ARB and dihydropyridine CCB is recommended in patients with cancer with systolic BP ≥ 160 mmHg and diastolic BP ≥ 100 mmHg.

• Diltiazem and verapamil are not recommended to treat arterial HTN in patients with cancer due to their drug–drug interaction.

BOX 2. Therapeutic goal for treating HTN caused by cancer treatment.

• A BP target of < 140 mmHg systolic and < 90 mmHg diastolic is recommended during cancer therapy.

• A BP target of < 130 mmHg systolic and < 80 mmHg diastolic may be considered during cancer therapy provided that the treatment is well tolerated.

• In selected asymptomatic patients with metastatic cancer, a systolic BP of 140–160 mmHg and diastolic BP of 90–100 mmHg treatment threshold may be considered provided there is ongoing BP monitoring.

• The competing cancer and CV risk evaluation is recommended if the systolic BP is ≥ 180 mmHg or diastolic BP ≥ 110 mmHg, and any cancer therapy associated with HTN should be deferred or temporarily withheld until the BP is controlled to values < 160 mmHg (systolic) and < 100 mmHg (diastolic).

Whether HTN per se or treatment with antihypertensive drugs influences the risk of cancer has been debated for many years. The 2023 ESH Guidelines acknowledge that certain antihypertensive drugs, including hydrochlorothiazide, may be associated with an increased risk of squamous cell carcinoma, consistent with the evidence reviewed above [115]. However, individual variability exists, and no substantial increase in the overall incidence of cancer has been demonstrated. Therefore, although the relatively short duration of the available trials, generally slightly more than 4 years, represents a limitation, the 2023 ESH Guidelines recommend that potential cancer risk should not be considered a barrier to the use of otherwise indicated antihypertensive therapy, including hydrochlorothiazide, which is frequently included in single‐pill combinations (SPCs) [115].

To reduce cancer risk and facilitate early cancer detection, both the general population and patients with HTN should receive appropriate education regarding guideline‐recommended cancer screening, with screening strategies tailored to age, sex, and other relevant risk factors. Healthy lifestyle behaviors should also be encouraged, including smoking cessation, limiting alcohol consumption, regular moderate‐intensity physical activity, and maintaining a balanced diet. Patients should additionally be encouraged to promptly seek medical evaluation for new or persistent symptoms to facilitate early detection and timely intervention. Tumor‐related biomarkers may provide additional information in selected clinical settings but should not replace established cancer screening strategies. When cancer is diagnosed, timely initiation of appropriate antineoplastic therapy is essential to prevent disease progression and potentially life‐threatening complications. At the same time, careful consideration should be given to the selection and administration of anticancer agents, particularly those associated with HTN or other forms of cardiovascular toxicity. For example, the cardiovascular risks of anti‐angiogenic agents should be carefully evaluated, with appropriate BP monitoring and management throughout treatment. In patients with coexisting HTN and cancer, multidisciplinary collaboration between oncology and cardiovascular specialists may be beneficial, particularly when BP remains difficult to control or when anticancer therapy poses substantial cardiovascular risks.

In addition to standardized BP assessment, cardiovascular biomarkers may provide complementary information for cardiovascular risk stratification in selected patients receiving potentially cardiotoxic cancer therapies. Cardiac troponin (cTn) reflects myocardial injury, whereas B‐type natriuretic peptide (BNP) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) provide information on myocardial wall stress and heart failure risk [119]. The 2022 ESC cardio‐oncology guideline incorporates cardiac troponin and natriuretic peptides into baseline cardiovascular risk assessment and longitudinal surveillance for selected anticancer therapies [117]. These biomarkers may help establish baseline cardiovascular status, identify patients at increased cardiovascular risk, and detect subclinical cardiovascular toxicity during treatment. Their interpretation is most informative when integrated with BP measurements, electrocardiography, and echocardiographic findings.

However, cardiac biomarker concentrations can be influenced by several non‐cardiac factors, including renal dysfunction, age, obesity, systemic inflammation, and pre‐existing cardiovascular disease. Therefore, isolated elevations should not be interpreted as definitive evidence of cancer treatment‐related cardiovascular injury without considering the broader clinical context. Serial measurements and comparison with baseline values are generally more informative than a single measurement.

Overall, the management of patients with coexisting HTN and cancer should integrate appropriate cancer prevention and screening, individualized antihypertensive and antineoplastic treatment, and systematic cardiovascular risk assessment. In this context, cTn and natriuretic peptides should be regarded as complementary tools rather than substitutes for standardized BP assessment or cardiovascular imaging. Further prospective studies are needed to determine their incremental prognostic value specifically in hypertensive cancer populations and to establish how cardiovascular biomarkers can be optimally integrated into individualized cardio‐oncology management.

7. Conclusion

Cancer and HTN frequently coexist and may interact through shared cardiometabolic risk factors, overlapping biological pathways, and treatment‐related cardiovascular toxicity. However, the available evidence does not support a uniform causal relationship across all malignancies. The observed association is likely to reflect a combination of shared risk factors, common biological mechanisms, and direct effects of cancer therapies.

The strongest evidence at the cancer–HTN interface currently concerns treatment‐related HTN, particularly that induced by VEGF/VEGFR pathway inhibition. Although treatment‐induced BP elevation may be associated with improved tumor outcomes in selected settings, it should not be regarded as universally beneficial or used to justify inadequate BP control. Emerging evidence concerning ICI‐based combination therapies further emphasizes the importance of individualized cardiovascular monitoring.

Evidence regarding antihypertensive medications and cancer risk remains heterogeneous. Randomized evidence does not demonstrate a consistent increase in overall cancer incidence with most major antihypertensive drug classes, whereas associations reported in observational studies may be influenced by confounding, tumor‐specific biology, treatment duration, and cumulative exposure. Accordingly, potential cancer‐related concerns should not override evidence‐based management of HTN.

Clinically, management should be integrated within the established framework of cardio‐oncology. Baseline cardiovascular risk assessment, standardized BP monitoring, timely antihypertensive treatment, appropriate use of CTCAE grading, and selective use of cardiovascular biomarkers can facilitate continuation of effective anticancer therapy while reducing cardiovascular complications.

Future research should prioritize prospective studies integrating longitudinal BP measurements, cancer subtype, anticancer drug exposure, cumulative antihypertensive exposure, metabolic factors, and cardiovascular biomarkers. Such studies are needed to distinguish causal relationships from shared confounding and to determine whether treatment‐induced HTN can serve as a reliable pharmacodynamic marker without compromising cardiovascular safety. Ultimately, an integrated cardio‐oncology approach that considers both tumor control and cardiovascular protection may improve long‐term outcomes in patients with cancer and HTN.

Author Contributions

Peizhi Jia: writing – original draft. Daxin Chen: writing – original draft. Jingting Wang: data curation, investigation. Yupei Guo: investigation. Jinhong Liu: investigation. Jiumao Lin: writing – review and editing, conceptualization.

Funding

This work was supported by the National Natural Science Foundation of China (No. 82004126 to Daxin Chen) and Collaborative Innovation Platform for R&D and Industrialization of Key Technologies in Chinese Patent Medicines in Fuzhou, Xiamen, and Quanzhou National Independent Innovation Demonstration Zone (No. 3502ZCQXT2023008 to Jiumao Lin).

Disclosure

This narrative review was designed to synthesize clinically and biologically relevant evidence concerning the cancer–HTN interface rather than to identify every publication containing the terms “cancer” and “hypertension.” PubMed was searched for English‐language publications from January 2002 through December 2025. The search strategy combined terms related to cancer and HTN with terms covering epidemiology, shared risk factors, obesity, metabolic syndrome, inflammation, RAAS, endothelial dysfunction, oxidative stress, angiogenesis, anticancer therapy, treatment‐related HTN, antihypertensive medications, cardiovascular toxicity, biomarkers, and cardio‐oncology.

Priority was given to prospective cohort studies, randomized controlled trials, systematic reviews and meta‐analyses, clinical guidelines, scientific statements, and recent clinically relevant studies. Experimental and mechanistic studies were included when they provided evidence directly relevant to the biological interaction between cancer and HTN.

Studies were selected according to their relevance to the central themes of the review, study design, methodological quality, clinical importance, and contribution to mechanistic understanding. Particular attention was given to the hierarchy of evidence and to potential confounding, reverse causation, heterogeneity among cancer types, and differences in treatment exposure. Reference lists of key reviews, guidelines, and selected primary studies were also examined to identify additional relevant publications.

Because this manuscript is a narrative review rather than a systematic review, formal PRISMA procedures and quantitative study screening were not performed. Nevertheless, the literature was selected using a structured and transparent approach, with emphasis on representative and clinically informative evidence rather than exhaustive retrieval of all potentially relevant publications.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Table S1: Common pathogenic mechanisms of cancer.

Table S2: Common pathogenic mechanisms of HTN.

Figure S1: The pathogenesis of cancer.

Figure S2: The pathogenesis of HTN.

Data Availability Statement

The authors have nothing to report.