ACE2 overexpression inhibits acquired platinum resistance-induced tumor angiogenesis in NSCLC

Cheng, Qin; Zhou, Ling; Zhou, Jianping; Wan, Huanying; Li, Qingyun; Feng, Yun

doi:10.3892/or.2016.4967

Cited by 36 publications

(35 citation statements)

References 19 publications

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“…Conversely, the activation of the alternative RAS, through Ang-(1–7) infusion or AT2R activation, can also reduce tumor growth. Cheng et al (2016) found that ACE2 overexpression may potentially suppress angiogenesis in non-small cell lung cancer (NSCLC) after the development of acquired platinum resistance. Namazi et al (2014) suggested that the combination of either captopril or captopril+losartan with innate and acquired tamoxifen resistance led to the prevention and even reversion of innate and acquired tamoxifen resistant phenotype.…”

Section: Introductionmentioning

confidence: 99%

The ACE2/Angiotensin-(1–7)/Mas Receptor Axis: Pleiotropic Roles in Cancer

Fan

et al. 2017

Front. Physiol.

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Cancer remains one of the most common causes of death and disability and represents a major economic burden in industrialized nations. The renin-angiotensin system (RAS) has been well-recognized as one of the most important regulators of both normal and pathological physiological processes in the brain, kidney, heart, and blood vessels. The activation of the angiotensin-converting enzyme 2/angiotensin-(1–7)/mitochondrial assembly receptor [ACE2/Ang-(1–7)/MasR] axis, which is one component of the RAS, has recently been identified as a critical component of pulmonary systems, gastric mucosa, and cancer. However, the ability of the ACE2/Ang-(1–7)/MasR axis to suppress or promote cancer has not been fully elucidated. In this review, we focus on recent experimental and clinical studies investigating the basic properties, roles, and mechanisms of ACE2, Ang-(1–7), and the MasR, as well as the axis pathway, to provide insights into possible therapeutic strategies for treating cancer that target the ACE2/Ang-(1–7)/MasR axis.

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Section: Introductionmentioning

confidence: 99%

The ACE2/Angiotensin-(1–7)/Mas Receptor Axis: Pleiotropic Roles in Cancer

Fan

et al. 2017

Front. Physiol.

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“…One potential explanation is that first‐line chemotherapy selects for tumors that are more susceptible to angiogenesis inhibitors. Consistent with this notion, there are preclinical data in several tumor types suggesting that platinum resistance enhances secretion of or dependence on angiogenic factors like VEGF . In addition, the chemotherapy backbone may modulate the effect of angiogenesis blockade, as ramucirumab has shown clinical benefit in combination with paclitaxel in EG cancer but not with platinum‐based regimens.…”

Section: Discussionmentioning

confidence: 84%

Regorafenib in Combination with First-Line Chemotherapy for Metastatic Esophagogastric Cancer

et al. 2019

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Background Angiogenesis is critical to gastroesophageal adenocarcinoma growth and metastasis. Regorafenib is a multikinase inhibitor targeting angiogenic and stromal receptor tyrosine kinases. We evaluated whether regorafenib augments the antitumor effect of first‐line chemotherapy in metastatic esophagogastric cancer. Materials and Methods Patients with previously untreated metastatic gastroesophageal adenocarcinoma received 5‐fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) every 14 days and regorafenib 160 mg daily on days 4 to 10 of each 14‐day cycle. The primary endpoint was 6‐month progression‐free survival (PFS). To identify predictive biomarkers of outcome, we examined correlations between genomic characteristics of sequenced pretreatment tumors and PFS. Results Between August 2013 and November 2014, 36 patients with metastatic esophagogastric cancer were accrued to this single‐center phase II study (NCT01913639). The most common grade 3–4 treatment‐related adverse events were neutropenia (36%), leucopenia (11%) and hypertension (8%). The 6‐month PFS was 53% (95% confidence interval [CI], 38%–71%), the objective response rate was 54% (95% CI, 37%–70%), and the disease control rate was 77% (95% CI, 67%–94%). Next‐generation sequencing did not identify any genomic alterations significantly correlated with response, and there was no association between homologous recombination deficiency and PFS with platinum‐based chemotherapy. Conclusion Regorafenib (one week on–one week off schedule) is well tolerated in combination with first‐line FOLFOX but does not improve 6‐month PFS relative to historical control. Implications for Practice Prognosis for metastatic esophagogastric cancer remains poor despite modern systemic therapy regimens. This phase II trial indicates that the combination of regorafenib and FOLFOX is well tolerated but does not add to the efficacy of first‐line chemotherapy in metastatic esophagogastric cancer. Notably, recently reported data suggest potential synergy between regorafenib and the PD‐1 inhibitor nivolumab. As this study demonstrates that regorafenib plus FOLFOX is safe, and combined chemotherapy and immunotherapy show favorable toxicity profiles, future studies combining immunotherapy with regorafenib and chemotherapy may be feasible.

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“…Indeed, serum VEGF levels were elevated in COVID-19 patients (Huang et al, 2020) possibly triggered by hypoxia and inflammatory changes and contributing to increased vascular permeability and pulmonary edema. Interestingly, increased ACE2 expression was shown to reduce VEGF production in vitro and in vivo (Cheng et al, 2016) ameliorating increased vascular permeability during lung injury (Yu et al, 2016) raising the question of whether SARS-CoV-2-induced endothelial ACE2 downregulation could underlie this observation. These findings highlight the importance of monitoring VEGF levels in patients with COVID-19 and also suggests a possibility of introducing treatment modalities to target VEGF responses.…”

Section: Ace2 and Cvd Symptoms In Covid-19 Patientsmentioning

confidence: 99%

Dysregulation of Angiotensin Converting Enzyme 2 Expression and Function in Comorbid Disease Conditions Possibly Contributes to Coronavirus Infectious Disease 2019 Complication Severity

et al. 2020

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ACE2 has emerged as a double agent in the COVID-19 ordeal being physiologically protective yet virally conducive. The identification of ACE2 in as many as 72 tissues suggests that extrapulmonary invasion and damage is likely, which indeed has already been demonstrated by cardiovascular and gastro-intestinal symptoms. On the other hand, identifying ACE2 dysregulation in patients with co-morbidities may offer insight as to why COVID-19 symptoms are often more severe in these individuals. This may be attributed to a pre-existing proinflammatory state that is further propelled with the cytokine storm induced by SARS-CoV-2 infection or the loss of functional ACE2 expression as a result of viral internalization. Here, we aim to characterize the distribution and role of ACE2 in various organs in order to highlight the scope of damage that may arise upon SARS-CoV-2 invasion. Furthermore, by examining the disruption of ACE2 in several co-morbid diseases, we offer insight into potential causes of increased severity of COVID-19 symptoms in certain individuals.

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ACE2 overexpression inhibits acquired platinum resistance-induced tumor angiogenesis in NSCLC

Cited by 36 publications

References 19 publications

The ACE2/Angiotensin-(1–7)/Mas Receptor Axis: Pleiotropic Roles in Cancer

The ACE2/Angiotensin-(1–7)/Mas Receptor Axis: Pleiotropic Roles in Cancer

Regorafenib in Combination with First-Line Chemotherapy for Metastatic Esophagogastric Cancer

Dysregulation of Angiotensin Converting Enzyme 2 Expression and Function in Comorbid Disease Conditions Possibly Contributes to Coronavirus Infectious Disease 2019 Complication Severity

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