The Effect of Renin–Angiotensin–Aldosterone System Inhibitors on Outcomes of Patients Treated with Immune Checkpoint Inhibitors: a Retrospective Cohort Study

Chiang, Cheng‐Yang; Wang, Shih-Syuan; Chang, Yu-Cheng; Chiang, Cho-Hsien; Chen, Chengying; Chen, Yuan-Jen; See, Xin Ya; Peng, C.-Y.; Hsia, Yuan Ping; Chiang, Chun‐Pin; Peng, Cheng-Ming

doi:10.1016/j.clon.2023.02.014

Cited by 7 publications

(13 citation statements)

References 26 publications

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“…Experimental studies have shown that the renin‐angiotensin‐aldosterone system (RAAS) plays an important role in regulating the immune response against tumor cells 12,13 . Consistent with preclinical data, clinical studies showed that patients who used ICI and RAASi had a higher rate of anti‐tumor effect survival than those who did not use RAASi 7,8,10,11,14 …”

Section: Introductionmentioning

confidence: 85%

“…In addition to novel drug discovery, repurposing existing drugs for new indications has become a cost‐effective strategy that can potentially improve the survival outcomes of cancer patients. 2 , 3 , 4 , 5 , 6 , 7 …”

Section: Introductionmentioning

confidence: 99%

“… 12 , 13 Consistent with preclinical data, clinical studies showed that patients who used ICI and RAASi had a higher rate of anti‐tumor effect survival than those who did not use RAASi. 7 , 8 , 10 , 11 , 14 …”

Section: Introductionmentioning

confidence: 99%

“…It is therefore imperative to develop strategies to augment and improve the response to ICI treatment. In addition to novel drug discovery, repurposing existing drugs for new indications has become a cost‐effective strategy that can potentially improve the survival outcomes of cancer patients 2–7 …”

Section: Introductionmentioning

confidence: 99%

“…Accumulating evidence from previous studies showed a trend of better survival outcomes in ICI patients who were concomitantly treated with certain medications, such as renin‐angiotensin‐aldosterone system inhibitors (RAASi) 3,7–11 . Experimental studies have shown that the renin‐angiotensin‐aldosterone system (RAAS) plays an important role in regulating the immune response against tumor cells 12,13 .…”

Section: Introductionmentioning

confidence: 99%

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The impact of peroxisome proliferator‐activated receptor‐γ activating angiotensin receptor blocker on outcomes of patients receiving immunotherapy

et al. 2023

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Background Certain angiotensin receptor blockers (ARBs) have peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) activation property, which has been associated with improved programmed cell death ligand 1 blockade and cytotoxic T lymphocyte‐mediated antitumor activity. Methods We conducted a retrospective cohort study to investigate the impact of PPAR‐γ‐activating ARBs on patient survival in patients treated with immune checkpoint inhibitors (ICIs) across all types of cancers. Results A total of 167 patients receiving both angiotensin receptor blockers (ARBs) and immune checkpoint inhibitors (ICIs) were included. Compared with non‐PPAR‐γ‐ARB users ( n = 102), PPAR‐γ‐ARB users ( n = 65) had a longer median overall survival (not reached [IQR, 16.0—not reached] vs. 18.6 [IQR, 6.1–38.6] months) and progression‐free survival (17.3 [IQR, 5.1—not reached] vs. 8.2 [IQR, 2.4–18.6] months). In Cox regression analysis, the use of PPAR‐γ‐activating ARBs had an approximately 50% reduction in all‐cause mortality and disease progression. Patients who received PPAR‐γ‐activating ARBs also had higher clinical benefit rates than non‐PPAR‐γ‐ARB users (82% vs. 61%, p = 0.005). Conclusion The use of ARBs with PPAR‐γ‐activating property is linked with better survival among patients receiving ICIs.

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Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The impact of peroxisome proliferator‐activated receptor‐γ activating angiotensin receptor blocker on outcomes of patients receiving immunotherapy

et al. 2023

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Statins as anti‐tumor agents: A paradigm for repurposed drugs

Tripathi,

Gupta,

Galande

2024

Cancer Reports

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BackgroundStatins, frequently prescribed medications, work by inhibiting the rate‐limiting enzyme HMG‐CoA reductase (HMGCR) in the mevalonate pathway to reduce cholesterol levels. Due to their multifaceted benefits, statins are being adapted for use as cost‐efficient, safe and effective anti‐cancer treatments. Several studies have shown that specific types of cancer are responsive to statin medications since they rely on the mevalonate pathway for their growth and survival.Recent FindingsStatin are a class of drugs known for their potent inhibition of cholesterol production and are typically prescribed to treat high cholesterol levels. Nevertheless, there is growing interest in repurposing statins for the treatment of malignant neoplastic diseases, often in conjunction with chemotherapy and radiotherapy. The mechanism behind statin treatment includes targeting apoptosis through the BCL2 signaling pathway, regulating the cell cycle via the p53‐YAP axis, and imparting epigenetic modulations by altering methylation patterns on CpG islands and histone acetylation by downregulating DNMTs and HDACs respectively. Notably, some studies have suggested a potential chemo‐preventive effect, as decreased occurrence of tumor relapse and enhanced survival rate were reported in patients undergoing long‐term statin therapy. However, the definitive endorsement of statin usage in cancer therapy hinges on population based clinical studies with larger patient cohorts and extended follow‐up periods.ConclusionsThe potential of anti‐cancer properties of statins seems to reach beyond their influence on cholesterol production. Further investigations are necessary to uncover their effects on cancer promoting signaling pathways. Given their distinct attributes, statins might emerge as promising contenders in the fight against tumorigenesis, as they appear to enhance the efficacy and address the limitations of conventional cancer treatments.

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Targeting the Renin–angiotensin–aldosterone System (RAAS) for Cardiovascular Protection and Enhanced Oncological Outcomes: Review

Pawlonka,

Buchalska,

Buczma

et al. 2024

Curr. Treat. Options in Oncol.

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Opinion statementThe renin–angiotensin–aldosterone system (RAAS) is a crucial regulator of the cardiovascular system and a target for widely used therapeutic drugs. Dysregulation of RAAS, implicated in prevalent diseases like hypertension and heart failure, has recently gained attention in oncological contexts due to its role in tumor biology and cardiovascular toxicities (CVTs). Thus, RAAS inhibitors (RAASi) may be used as potential supplementary therapies in cancer treatment and CVT prevention. Oncological treatments have evolved significantly, impacting patient survival and safety profiles. However, they pose cardiovascular risks, necessitating strategies for mitigating adverse effects. The main drug classes used in oncology include anthracyclines, anti-HER2 therapies, immune checkpoint inhibitors (ICIs), and vascular endothelial growth factor (VEGF) signaling pathway inhibitors (VSPI). While effective against cancer, these drugs induce varying CVTs. RAASi adjunctive therapy shows promise in enhancing clinical outcomes and protecting the cardiovascular system. Understanding RAAS involvement in cancer and CVT can inform personalized treatment approaches and improve patient care.

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The Effect of Renin–Angiotensin–Aldosterone System Inhibitors on Outcomes of Patients Treated with Immune Checkpoint Inhibitors: a Retrospective Cohort Study

Cited by 7 publications

References 26 publications

The impact of peroxisome proliferator‐activated receptor‐γ activating angiotensin receptor blocker on outcomes of patients receiving immunotherapy

The impact of peroxisome proliferator‐activated receptor‐γ activating angiotensin receptor blocker on outcomes of patients receiving immunotherapy

Statins as anti‐tumor agents: A paradigm for repurposed drugs

Targeting the Renin–angiotensin–aldosterone System (RAAS) for Cardiovascular Protection and Enhanced Oncological Outcomes: Review

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