Angiotensin receptor blocker use and gastro‐oesophageal cancer survival: a population‐based cohort study

Busby, John; McMenamin, Úna C.; Spence, Andrew; Johnston, Brian T.; Hughes, Carmel; Cardwell, Christopher

doi:10.1111/apt.14388

Cited by 32 publications

(23 citation statements)

References 48 publications

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“…The degree of desmoplasia is related to disease progression [14,24]. Angiotensin II receptor agonists commonly used for treatment of high pressure, including Food and Drug Administration (FDA) approved Losartan, Candersartan, Olmesartan or Valssartan, were shown to be effective in reducing mortality of gastro-esophageal cancer patients [27]. The inhibition of the transforming growth factor-β (TGF-β) signaling pathway mediated by Losartan and its analogs results in a reduced secretion of collagen I and consequently reduced desmoplasia, improving the delivery of chemotherapeutics to tumor cells [28,29].…”

Section: Targeting the Tumor Microenvironmentmentioning

confidence: 99%

Targeting Tumor Microenvironment for Cancer Therapy

Roma‐Rodrigues

Mendes

Baptista

et al. 2019

IJMS

913

683

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Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response from neighbor stromal cells (e.g., fibroblasts) and immune cells (lymphocytes and macrophages), inducing angiogenesis and, ultimately, resulting in metastasis. Exosomes secreted by TME cells are central players in all these events. The TME profile is preponderant on prognosis and impacts efficacy of anti-cancer therapies. Hence, a big effort has been made to develop new therapeutic strategies towards a more efficient targeting of TME. These efforts focus on: (i) therapeutic strategies targeting TME components, extending from conventional therapeutics, to combined therapies and nanomedicines; and (ii) the development of models that accurately resemble the TME for bench investigations, including tumor-tissue explants, “tumor on a chip” or multicellular tumor-spheroids.

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Section: Targeting the Tumor Microenvironmentmentioning

confidence: 99%

Targeting Tumor Microenvironment for Cancer Therapy

Roma‐Rodrigues

Mendes

Baptista

et al. 2019

IJMS

913

683

View full text Add to dashboard Cite

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“…Renin-angiotensin system mainly controls blood pressure; however, cancer cells and their microenvironment also express renin and angiotensin, which play a pathophysiological role in cancer development [ 32 ]. Several clinical studies have demonstrated that taking ARBs could decrease the risk of developing cancers [ 33 , 34 ]. In vitro and in vivo studies have further revealed that these anticancer effects of ARB include direct suppression of cancer growth and increase of antitumor immunity [ 35 – 38 ].…”

Section: Immunomodulatory Effects Of Drugs Used For Treating Commomentioning

confidence: 99%

Immunomodulatory Effects of Drugs for Effective Cancer Immunotherapy

Matsushita

Kawaguchi

2018

Journal of Oncology

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Recent advances in cancer immunotherapy, including immune checkpoint inhibitors or adoptive T cell therapies, have contributed to better outcomes in cancer patients. However, there are still many cancers with no cure. Therefore, combinations of several treatment strategies are being explored, and enhancing anticancer immunity will play an important role to combat the disease. There have been several reports on the immune-modulatory effects of commonly used drugs, namely, statin, metformin, and angiotensin receptor blockers (ARBs), which suggest that these drugs could enhance immunity against cancer cells. Other anticancer drugs, such as anthracyclines, thalidomides, lenalidomides, and hypomethylating drugs, could also strengthen the immune system to attack cancer cells at a relatively low dose. Hence, these drugs might contribute to better outcomes in cancer patients.

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“…In addition to other biological factors, exosomes secreted by cancer and TME cells modulate stromal cells residing in the TME [220,221]. Understanding such changes in the TME during tumor progression will yield additional advantages in the development of novel therapeutic strategies to tackle cancer progression and metastasis compared to the currently available options, for example, by targeting the ECM by using angiotensin II, TGF-β, and heparanase inhibitor roneparstat (SST0001) [222][223][224][225][226], affecting hypoxia and acidosis by targeting hypoxia-induced factor-1 (HIF-1) using several compounds and therapies such as Topotecan [227][228][229], and targeting endothelial cells and pericytes to avoid neovascularization using several antiangiogenic drugs such as bevacizumab (Avastin) [230,231]. In addition, targeting the recruitment of tumor-associated-macrophages (TMAs) in the TME [232], activating the anti-tumor activity of immune cells [233], and targeting CAFs [230] might add new therapeutic benefits in the treatment of tumors in advanced stages.…”

Section: Targeting the Tumor Microenvironmentmentioning

confidence: 99%

Exosomes are the Driving Force in Preparing the Soil for the Metastatic Seeds: Lessons from the Prostate Cancer

Saber

Ali

Gaballa

et al. 2020

Cells

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Exosomes are nano-membrane vesicles that various cell types secrete during physiological and pathophysiological conditions. By shuttling bioactive molecules such as nucleic acids, proteins, and lipids to target cells, exosomes serve as key regulators for multiple cellular processes, including cancer metastasis. Recently, microvesicles have emerged as a challenge in the treatment of prostate cancer (PCa), encountered either when the number of vesicles increases or when the vesicles move into circulation, potentially with an ability to induce drug resistance, angiogenesis, and metastasis. Notably, the exosomal cargo can induce the desmoplastic response of PCa-associated cells in a tumor microenvironment (TME) to promote PCa metastasis. However, the crosstalk between PCa-derived exosomes and the TME remains only partially understood. In this review, we provide new insights into the metabolic and molecular signatures of PCa-associated exosomes in reprogramming the TME, and the subsequent promotion of aggressive phenotypes of PCa cells. Elucidating the molecular mechanisms of TME reprogramming by exosomes draws more practical and universal conclusions for the development of new therapeutic interventions when considering TME in the treatment of PCa patients.

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Angiotensin receptor blocker use and gastro‐oesophageal cancer survival: a population‐based cohort study

Abstract: In this large population-based gastro-oesophageal cancer cohort, we found moderately reduced cancer-specific mortality among ARB users. However, confirmation in further independent epidemiological studies with sufficient staging information is required.

Cited by 32 publications

References 48 publications

Targeting Tumor Microenvironment for Cancer Therapy

Targeting Tumor Microenvironment for Cancer Therapy

Immunomodulatory Effects of Drugs for Effective Cancer Immunotherapy

Exosomes are the Driving Force in Preparing the Soil for the Metastatic Seeds: Lessons from the Prostate Cancer

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