Potential role of Aliskiren in cancer modulation compared to other Renin-Angiotensin inhibitors: an in-depth review

BACKGROUND: Renin Angiotensin System inhibitors (RASi) are widely used in cancer patients to treat high prevalence comorbidities such as hypertension, proteinuric nephropathies and cardiopathies. Emerging research has raised concerns about their potential role in oncogenesis, while uncovering promising anti-tumor properties. OBJECTIVE: This systematic review investigates the effects of RASi, specifically angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), and the direct renin inhibitor (DRI) Aliskiren, on cancer risk and progression. Emphasis is placed on underlying molecular pathways and potential impact of RASi on cancer development and growth. RESULTS: Evidence from the analyzed studies remains heterogeneous. ACEi and ARBs may contribute to oncogenic processes through bradykinin accumulation and renin activation, both of which are known to drive mechanisms associated with cancer development and progression, particularly in lung cancer. Conversely, Aliskiren may potentially exhibit a more favorable anticancer profile by interfering with neo-angiogenesis, oxidative stress, inflammatory signaling, tumor growth, and metastasis. Moreover, existing studies suggest that Aliskiren may help reduce cancer cachexia, further supporting its potential relevance in oncologic settings, although the available literature on Aliskiren remains limited. CONCLUSION: While the oncogenic effects of ACEi and ARBs on cancer remain inconclusive, Aliskiren emerges as an antihypertensive drug potentially able to interfere with pro-oncogenic signaling. Nonetheless, its limited evidence base underscores the urgent need for well-designed prospective studies to clarify the differential oncologic impact of various RASi classes across populations. Indeed, cancer patients undergoing long-term RASi deserve close monitoring and multidisciplinary approach for assessment of personalized therapy.