Enhancing the Anti-angiogenic Effect of Bevacizumab with ACE Inhibition on mCRC

Erdat, Efe Cem; Köksoy, Elif Berna; Utkan, Güngör

doi:10.1007/s12029-022-00890-4

Cited by 3 publications

(2 citation statements)

References 19 publications

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“…(41) In metastatic colorectal cancer, patients using ACEi for hypertension and treated with bevacizumab showed a higher disease-free survival suggesting that ACEi could enhance the antiangiogenic effect of VEGF-a blockade. (42) In early-stage and left-sided CRCs, ACEi was associated with reduced risk of disease recurrence. (43) ACE expression in immune cells has been reported (19,20,21) and the overexpression of ACE in mice macrophages or neutrophils has been linked to a higher resistance to conditions that are common in old adults such as tumors, infections, chronic neurotoxicity and neuroin ammation.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin converting enzyme expression on circulating immune cells from colorectal cancer patients correlates with the disease stage. Results from a preliminary study.

Bueno,

Frasca,

Forones

2024

Preprint

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Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related mortality worldwide. Because CRC is a very complex disease, sometimes patients at same disease stage are treated with combinations of systemic therapy and surgery leading to different outcomes. Immune T and B cells infiltrating the tumor has been associated with disease-free survival, cancer-specific survival and overall survival. In the opposite, Myeloid-derived suppressor cells infiltrating the tumor has been linked to poor outcome. The peripheral blood evaluation of immune cells is less invasive, easy to be performed in different CRC follow-up visits, and could be used as a guide for therapy interventions. The expression of angiotensin converting enzyme (ACE) in immune cells can be used as a biomarker for cancer prognosis an also as a target for cancer treatment since ACE expression in macrophages and neutrophils has been related to improved immunity. Our aim therefore was to investigate the expression of ACE in subsets of T, B, and myeloid-derived suppressor cells in peripheral blood from CRC patients. We found that the expression of ACE is increased in Naïve and Effector T cells and in Effector B cells of CRC patients stage III. These findings open opportunities for targeting ACE in immune cells as a new therapy in colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

Angiotensin converting enzyme expression on circulating immune cells from colorectal cancer patients correlates with the disease stage. Results from a preliminary study.

Bueno,

Frasca,

Forones

2024

Preprint

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“…Therefore, it seems that ACE-Is in combination with platinum constitute the most promising chemotherapeutic protocol to be extrapolated to other vulnerable malignancies, such as ovarian cancer. Furthermore, ACE-Is co-administered with anti-VEGF agents, also improved survival in metastatic renal cell cancer [ 38 – 40 ], metastatic colorectal cancer [ 35 , 41 ], glioblastoma [ 42 ], advanced hepatocellular carcinoma [ 35 ] and non-small cell lung cancer [ 43 , 44 ] probably through their additive antiangiogenic activity. On the contrary, in a secondary pooled analysis of two phase III randomized controlled trials, RAS-modulating agents had no effect on survival of metastatic renal cell carcinoma patients treated with anti-VEGF agents [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-converting enzyme inhibitors for ovarian cancer? — a new adjuvant option or a silent trap

Regulska,

Michalak,

Kolenda

et al. 2023

Rep Pract Oncol Radiother.

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Background Ovarian cancer is a huge therapeutic and financial problem for which approved treatments have already achieved their limit of efficiency. A cost-effective strategy to extend therapeutic options in this malignancy is drug repurposing aimed at overcoming chemoresistance. Here, angiotensin-converting enzyme inhibitors (ACE-I) are worth considering. Materials and methods We searched literature for publications supporting the idea of adjuvant application of ACE-Is in ovarian malignancy. Then, we searched The Cancer Genome Atlas databases for relevant alternations of gene expression patterns. We also performed in silico structure-activity relationship evaluation for predicting ACE-Is’ cytotoxicity against ovarian cancer cell lines. Finally, we reviewed the potential obstacles in ACE-Is repurposing process. Results The alternation of angiotensin receptor expression in ovarian cancer translates into poorer patient survival. This confirms the participation of the renin-angiotensin system in ovarian carcinogenesis. In observational studies, ACE-Is were shown synergize with both, platinum-based chemotherapy as well as with antiangiogenic therapy. Consistently, our in silico simulation showed that ACE-Is are probably cytotoxic against ovarian cancer cells. However, the publications on their chemopreventive properties were inconclusive. In addition, some reports correlated ACE-Is use with increased general cancer incidence. We hypothesized that this effect could be associated with mutagenic nitrosamine formation in ACE-Is’ pharmaceutical formulations, as was the case with angiotensin receptor blockers (ARBs) and other well-established pharmaceuticals. Conclusions Available data warrant further research into repositioning ACE-Is to ovarian cancer as chemosensitizers. Prior to this, however, a special research program is needed to detect possible genotoxic contaminants of ACE-Is.

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Anticancer Potential of ACEIs/ARBs Administration in Colorectal Cancer

Wang,

Jing

2024

CMC

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Background:: Colorectal cancer (CC) is the fourth most common type of cancer that causes illness and death. Medicines like ACE inhibitors and ARBs, usually used for heart problems, have shown they might help with the growth and development of CC. Introduction:: An analysis of ACE inhibitors and colon cancer is conducted in this comprehensive review. The main goal is to see how ACEIs/ARBs affect the chances of getting cancer and dying in patients with CC. Methods:: A systematic literature search was conducted to identify relevant studies. Inclusion criteria encompassed studies that evaluated the use of ACEIs/ARBs in patients with CC and reported outcomes related to new cancer incidence and mortality. Data from selected studies were extracted and analyzed using appropriate statistical methods. Results:: The study showed that fewer cancer cases occurred in patients who took ACEIs/ARBs compared to those who did not (RR 0.962, 95% CI 0.934-0.991, p = 0.010). Furthermore, patients with CC who utilized ACEIs/ARBs exhibited a decreased mortality rate compared to non-users (HR 0.833, 95% CI 0.640-1.085, p = 0.175). Conclusion:: This review suggests that using ACEIs/ARBs medicine could help people with CC live longer and lower their chances of dying. These results highlight the potential benefits of utilizing ACE inhibitors in the management of CC, warranting further investigation and consideration in clinical practice.

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Enhancing the Anti-angiogenic Effect of Bevacizumab with ACE Inhibition on mCRC

Cited by 3 publications

References 19 publications

Angiotensin converting enzyme expression on circulating immune cells from colorectal cancer patients correlates with the disease stage. Results from a preliminary study.

Angiotensin converting enzyme expression on circulating immune cells from colorectal cancer patients correlates with the disease stage. Results from a preliminary study.

Angiotensin-converting enzyme inhibitors for ovarian cancer? — a new adjuvant option or a silent trap

Anticancer Potential of ACEIs/ARBs Administration in Colorectal Cancer

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