Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial

Burn, John; Sheth, Harsh; Elliott, Faye; Reed, Lynn; Macrae, Finlay; Mecklin∥, Jukka–Pekka; Möslein, Gabriela; McRonald, Fiona E.; Bertario, Lucio; Evans, D. Gareth; Gerdes, Anne-Marie; Ho, Judy W. C.; Lindblom, Annika; Morrison, Patrick J.; Rashbass, Jem; Ramesar, Raj; Seppälä, Toni T.; Thomas, Huw; Pylvänäinen, Kirsi; Borthwick, Gillian M.; Mathers, John C.; Bishop, D. Timothy; Boussioutas, Alex; Brewer, Carole; Cook, Jackie; Eccles, Diana; Ellis, Anthony; Hodgson, Shirley; Lubiński, Jan; Maher, Eamonn R.; Porteous, Mary; Sampson, Julian R.; Scott, Rodney J.; Side, Lucy

doi:10.1016/s0140-6736(20)30366-4

Cited by 267 publications

(214 citation statements)

References 30 publications

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“…An RCT 76,85,90 showed that 600 mg acetylsalicylic acid daily for 2-4 years was well tolerated and reduced colorectal cancer incidence after 5 years following initiation of the treatment. A recently published study 91 has shown that the benefit of prevention with acetylsalicylic acid persists into the second decade. Observational data in the general population suggest that lower doses may also be effective 92,93 .…”

Section: Conclusion and Recommendationsmentioning

confidence: 99%

European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender

Seppälä

Latchford

Negoi

et al. 2021

British Journal of Surgery

160

148

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Background: Lynch syndrome is the most common genetic predisposition for hereditary cancer but remains underdiagnosed. Large prospective observational studies have recently increased understanding of the effectiveness of colonoscopic surveillance and the heterogeneity of cancer risk between genotypes. The need for gene-and gender-specific guidelines has been acknowledged. Methods: The European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP) developed a multidisciplinary working group consisting of surgeons, clinical and molecular geneticists, pathologists, epidemiologists, gastroenterologists, and patient representation to conduct a graded evidence review. The previous Mallorca guideline format was used to revise the clinical guidance. Consensus for the guidance statements was acquired by three Delphi voting rounds. Results: Recommendations for clinical and molecular identification of Lynch syndrome, surgical and endoscopic management of Lynch syndrome-associated colorectal cancer, and preventive measures for cancer were produced. The emphasis was on surgical and gastroenterological aspects of the cancer spectrum. Manchester consensus guidelines for gynaecological management were endorsed. Executive and layperson summaries were provided. Conclusion: The recommendations from the EHTG and ESCP for identification of patients with Lynch syndrome, colorectal surveillance, surgical management of colorectal cancer, lifestyle and chemoprevention in Lynch syndrome that reached a consensus (at least 80 per cent) are presented.

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Section: Conclusion and Recommendationsmentioning

confidence: 99%

European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender

Seppälä

Latchford

Negoi

et al. 2021

British Journal of Surgery

160

148

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“…Aspirin is a potent suppressor of prostaglandins and thromboxane A2 (TXA2) generation due to its irreversible inactivation of the cyclooxygenase (COX) enzyme, yielding anti-inflammatory and anti-thrombotic effects, respectively [ 199 ]. In addition of its regular use to prevent cardiovascular disease in those at high risk, aspirin may prevent gastrointestinal tract cancers [ 200 – 202 ] and participate in a wide range of different disorders [ 203 ], although its effects are highly dependent on the timing and dose administered [ 204 ]. While low doses aspirin may play indirect beneficial effects in the RAAS, including suppression of angiotensin II actions, high doses (> 200 mg/day) may hamper cardioprotective and lung-protective effects of the majority of drugs that address RAAS [ 205 – 207 ].…”

Section: Main Textmentioning

confidence: 99%

Repurposing existing drugs for COVID-19: an endocrinology perspective

Cadegiani

2020

BMC Endocr Disord

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Background Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2. Main text While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed. Conclusion While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.

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“…A preclinical study found NO-donating aspirin, acetylsalicyclic acid (NCX-4016), provides protection against aspirin-induced gastric damage. In 2020, a 10-year follow-up study concluded that taking 600 mg aspirin for at least 2 years significantly reduces the incidence of colon cancer in people who are carriers of Lynch syndrome [154]. These findings suggest that NO-donating aspirin might be a good candidate for CRC therapy.…”

Section: Clinical Manifestation Of No/nos In Colon Cancermentioning

confidence: 99%

Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer

Wang

Xie

et al. 2020

Cancers

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Colorectal cancer (CRC) is one of the most lethal malignancies worldwide and CRC therapy remains unsatisfactory. In recent decades, nitric oxide (NO)—a free-radical gas—plus its endogenous producer NO synthases (NOS), have attracted considerable attention. NO exerts dual effects (pro- and anti-tumor) in cancers. Endogenous levels of NO promote colon neoplasms, whereas exogenously sustained doses lead to cytotoxic functions. Importantly, NO has been implicated as an essential mediator in many signaling pathways in CRC, such as the Wnt/β-catenin and extracellular-signal-regulated kinase (ERK) pathways, which are closely associated with cancer initiation, metastasis, inflammation, and chemo-/radio-resistance. Therefore, NO/NOS have been proposed as promising targets in the regulation of CRC carcinogenesis. Clinically relevant NO-donating agents have been developed for CRC therapy to deliver a high level of NO to tumor sites. Notably, inducible NOS (iNOS) is ubiquitously over-expressed in inflammatory-associated colon cancer. The development of iNOS inhibitors contributes to targeted therapies for CRC with clinical benefits. In this review, we summarize the multifaceted mechanisms of NO-mediated networks in several hallmarks of CRC. We review the clinical manifestation and limitations of NO donors and NOS inhibitors in clinical trials. We also discuss the possible directions of NO/NOS therapies in the immediate future.

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Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial

Cited by 267 publications

References 30 publications

European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender

European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender

Repurposing existing drugs for COVID-19: an endocrinology perspective

Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer

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