Long-term aspirin use for primary cancer prevention: An updated systematic review and subgroup meta-analysis of 29 randomized clinical trials

Wu, Qibiao; Yao, Xiaojun; Chen, Hongwei; Liu, Zheng‐Tang; Li, Ting; Fan, Xing‐Xing; Zhang, Guilin; Yu, Lili; Chen, Min; Xu, Cong; Zhang, Ruonan; Bi, Chen; Sui, Xinbing; Leung, Elaine Lai‐Han

doi:10.7150/jca.49001

Cited by 15 publications

(12 citation statements)

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“…Indeed, there are clinical meta-analysis suggesting that the use of a low-dose aspirin in the primary prevention reduces the risk of cancer diagnosis ( 45 , 46 ). However, more studies are needed as more recent publications seem to show that not all cancers respond in a similar way to aspirin-mediated platelet inhibition; and that side effects of a long-term aspirin intake could be an important cause of patient morbidity ( 17 , 18 ).…”

Section: Discussionmentioning

confidence: 99%

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P2RY12-Inhibitors Reduce Cancer-Associated Thrombosis and Tumor Growth in Pancreatic Cancers

et al. 2021

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Platelet function can be modified by cancer cells to support tumor growth, causing alterations in the delicate hemostatic equilibrium. Cancer-cell and platelet interactions are one of the main pillars of Trousseau’s syndrome: a paraneoplastic syndrome with recurring and migrating episodes of thrombophlebitis. Altogether, this leads to a four-fold risk of thrombotic events in cancer patients, which in turn, portend a poor prognosis. We previously demonstrated that anti-P2RY12 drugs inhibit cancer-associated-thrombosis and formation of tumor metastasis in pancreatic cancer models. Here, we aimed to (1) compare the effects of aspirin and clopidogrel on pancreatic cancer prevention, (2) characterize the effects of clopidogrel (platelet P2RY12 inhibitor) on cancer-associated thrombosis and cancer growth in vivo, (3) determine the effect of P2RY12 across different digestive-tract cancers in vitro, and (4) analyze the expression pattern of P2RY12 in two different cancer types affecting the digestive system. Clopidogrel treatment resulted in better survival rates with smaller primary tumors and less metastasis than aspirin treatment. Clopidogrel was also more effective than aspirin at dissolving spontaneous endogenous thrombi in our orthotopic advanced cancer mouse model. P2RY12 expression gives pancreatic adenocarcinomas proliferative advantages. In conclusion, we propose the hypothesis that clopidogrel should be further studied to target and prevent Trousseau’s syndrome; as well as diminish cancer growth and spread. However, more studies are required to determine the implicated pathways and effects of these drugs on cancer development.

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Section: Discussionmentioning

confidence: 99%

“…Aspirin prevents the formation of thromboxane A2 (TXA2), a platelet agonist, and at a high concentration, may also limit inflammation (14)(15)(16). Different retrospective studies have shown the benefit of long-term Aspirin treatment on digestive-tract cancer development and formation of distant metastasis (17,18).…”

Section: Introductionmentioning

confidence: 99%

P2RY12-Inhibitors Reduce Cancer-Associated Thrombosis and Tumor Growth in Pancreatic Cancers

et al. 2021

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“…Substantial heterogeneity will be considered when I 2 > 50% or P < .1. [40][41][42][43] 2.4.3. Data synthesis.…”

Section: Assessment Of Risk Of Bias In Included Studiesmentioning

confidence: 99%

“…If the hypothesis of homogeneity is not rejected, a fixed-effects model will be used to estimate the summary RR (OR or RD), WMD (or SMD) and 95% CI; otherwise, a randomeffects model will be used. [40][41][42][43][44] If quantitative synthesis is inappropriate, we will provide a systematic narrative synthesis with the information presented to summarize and explain the characteristics and findings of the included studies. [45] The strength of the evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation working group methodology (GRADE).…”

Section: Assessment Of Risk Of Bias In Included Studiesmentioning

confidence: 99%

Compound Kushen injection plus platinum-based chemotherapy for stage IIIB/IV non-small cell lung cancer

Chen

Yao

et al. 2019

Medicine

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Background: Compound Kushen injection (CKI) is a commonly used anti-tumor Chinese patent medicine, which is extracted from Kushen (Radix Sophorae Flavescentis) and Baituling (Rhizoma Smilacis Glabrae) and has been widely prescribed as an add-on therapy to platinum-based chemotherapy (PBC) for advanced non-small cell lung cancer (NSCLC). However, the efficacy and safety of this combination therapy remain controversial.Methods and analysis: A systematic review and meta-analysis will be performed following the PRISMA (Preferred Reported Items for Systematic Review and Meta-analysis) guidelines. All randomized controlled trials (RCTs) comparing CKI in combination with PBC versus PBC alone will be retrieved and assessed for inclusion. Analyses will be performed using Review Manager 5.3, Comprehensive Meta-Analysis 3.0 and Trial Sequential Analysis software. The disease control rate (DCR) will be defined as the primary outcome, and the objective response rate (ORR), quality of life (QOL), survival rate, and toxicities will be the secondary outcomes.Results: This study will systematically evaluate the efficacy and safety of Compound Kushen injection combined with platinumbased chemotherapy in the treatment of stage III/IV NSCLC. The results of this study will be published in a peer-reviewed journal.Conclusions: This systematic review and meta-analysis of eligible randomized controlled trials will evaluate the effects of Compound Kushen injection as adjunctive therapy to platinum-based chemotherapy in patients with stage III/IV non-small cell lung cancer, thus providing evidence to the clinical use of this combination therapy for the specific subsets of patients. PROSPERO registration number: CRD42019134892Abbreviations: CI = confidence interval, CKI = compound Kushen injection, CMA = comprehensive meta-analysis, CNKI = China National Knowledge Infrastructure, DCR = disease control rate, ITT = intention-to-treat, NSCLC = non-small cell lung cancer, OR = odds ratio, ORR = objective response rate, PBC = platinum-based chemotherapy, QOL = quality of life, RCT = randomized controlled trial, RD = risk difference, RIS = required information size, RM = review manager, RR = risk ratio, SMD = standardized mean difference, TSA = trial sequential analysis, WHO = World Health Organization, WMD = weighted mean difference.

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“…Globally, lung cancer remains the commonest cancer and the leading cause of cancer death. Non-small cell lung cancers (NSCLC) is the most prevalent type, accounting for approximately 85% of lung cancers, and most newly diagnosed NSCLC patients are already at advanced stages 1 , 2 , 3 , 4 when it is often too late for surgery. For the NSCLC patients with epidermal growth factor receptor (EGFR) mutation, tyrosine kinase inhibitors (TKIs) are the first-line treatment of choice 5 and greatly improve the outcome of patients.…”

Section: Introductionmentioning

confidence: 99%

β-elemene enhances the antitumor activity of erlotinib by inducing apoptosis through AMPK and MAPK pathways in TKI-resistant H1975 lung cancer cells

Wang¹,

Xu²,

Chen³

et al. 2021

J. Cancer

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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) significantly improve the outcome of non-small-cell lung cancer (NSCLC) patients with EGFR mutations, however, most TKI-treated patients will develop resistance to TKIs. β-elemene, extracted from Curcuma aromatica Salisb., has been widely used to treat various malignant tumors, including TKI-resistant NSCLC, but, the effects and the molecular mechanisms remain unclear. In this study, the NCI-H1975 cell line harboring double mutations L858R/T790M was treated with varying concentrations of β-elemene and/or erlotinib. The effects of β-elemene on cell proliferation, migration, apoptosis, and the expression of relevant proteins of NCI-H1975 cells were evaluated. The results revealed that β-elemene significantly inhibited the growth, colony formation capacity, wound healing ability of NCI-H1975 cells, and improved the sensitivity of NCI-H1975 cells to erlotinib. Compared with erlotinib alone, β-elemene plus erlotinib significantly promoted the apoptosis of NCI-H1975 cells, accompanied by the down-regulated expression of P-mTOR, P-EGFR, CHOP proteins and up-regulated expression of P-AMPKα and Bax proteins. Taken together, these findings demonstrate that β-elemene suppresses the proliferation and migration of TKI-resistant H1975 cells, and enhances the antitumor activity of erlotinib by inducing apoptosis through AMPK and MAPK pathways in TKI-resistant H1975 lung cancer cells, indicating that β-elemene is a promising anti-cancer therapeutic candidate for TKI-resistant NSCLC.

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Long-term aspirin use for primary cancer prevention: An updated systematic review and subgroup meta-analysis of 29 randomized clinical trials

Cited by 15 publications

References 77 publications

P2RY12-Inhibitors Reduce Cancer-Associated Thrombosis and Tumor Growth in Pancreatic Cancers

P2RY12-Inhibitors Reduce Cancer-Associated Thrombosis and Tumor Growth in Pancreatic Cancers

Compound Kushen injection plus platinum-based chemotherapy for stage IIIB/IV non-small cell lung cancer

β-elemene enhances the antitumor activity of erlotinib by inducing apoptosis through AMPK and MAPK pathways in TKI-resistant H1975 lung cancer cells

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