A potential role for aspirin in the prevention and treatment of cholangiocarcinoma

Abstract

Cholangiocarcinoma is the second most common primary hepatic cancer, with a rising incidence worldwide. Owing to late diagnosis and limited treatment options, the prognosis for cholangiocarcinoma remains dismal, compelling a search for new treatments. As aspirin exhibits a well‐supported chemopreventive effect on common cancers, researchers have proposed using aspirin as a potential preventive and adjuvant agent for cholangiocarcinoma. In the present review of the literature, we provide a background on cholangiocarcinoma and potential mechanisms of action underlying the anticancer effect of aspirin. Although the exact mode of action remains unclear, multiple downstream effects of aspirin may interfere with cholangiocarcinogenesis, tumour growth and metastasis—including inhibiting the COX‐2 pathway, preventing platelet aggregation and modulating certain proteins and signalling. This review also summarises evidence to support the chemopreventive effects of aspirin on common cancers, particularly colorectal cancer and discusses studies that report a positive outcome of aspirin in cholangiocarcinoma. Regular use of aspirin is associated with a reduced incidence of colorectal cancers as well as cholangiocarcinomas, and improved survival. Aspirin thus appears to play a role in the primary prevention and treatment of cholangiocarcinoma. However, further studies are needed to confirm these benefits and to establish a cause‐and‐effect relationship.

Tegaserod Maleate Inhibits Esophageal Squamous Cell Carcinoma Proliferation by Suppressing the Peroxisome Pathway

“…It is advantageous to find a new anticancer use among existing drugs that may already have an established safety profile ( 19 ). NSAIDS, such as aspirin, have been found lower risk of cholangiocarcinoma and colorectal cancer ( 20 , 21 ). Not only that, but there is a strong interest in reusing metformin to prevent cancer and cancer recurrence ( 22 ).…”

Current Therapeutics in Primary Sclerosing Cholangitis

“…118 It acts via inhibition of the cyclooxygenase-2 pathway resulting in reduction of carcinogenic prostaglandin E2, 118 which is of relevance to PSC-related CCA where overexpression of cyclooxygenase-2 in biliary epithelium has been described. 3,118 It also reduces platelet aggregation with a negative impact on tumor angiogenesis and metastases, and cellular inhibition of signaling pathways that promote tumor growth. 118 Evidence for aspirin use in reduction of CCA risk is growing, [118][119][120][121] however studies investigating this specifically in PSC is lacking.…”

“…3,118 It also reduces platelet aggregation with a negative impact on tumor angiogenesis and metastases, and cellular inhibition of signaling pathways that promote tumor growth. 118 Evidence for aspirin use in reduction of CCA risk is growing, [118][119][120][121] however studies investigating this specifically in PSC is lacking. 122 A retrospective cohort study published in abstract form demonstrated a trend toward significant reduction in risk of PSC-related CCA with aspirin use only.…”

Synthesis, crystal structure and in vitro anti-proliferative activity of 2-[(4-acetylphenyl)carbamoyl]phenyl acetate

“…Aspirin has emerged as a promising intervention in cancer treatment in the past decade (Tran et al, 2021;Lichtenberger et al, 2019), and has a protective effect against several types of cancer (Garcia-Albeniz et al, 2011;Usman et al, 2015). It induces cell death in various cancer cell lines, such as myeloid leukaemia and HeLa cells, chronic lymphocytic leukaemia cells, colon cancer cells (Bellosillo et al, 1998), gastric cancer (Gu et al, 2005), colorectal cancer (Stark et al, 2007) and cholangiocarcinoma (Shen & Shen, 2021).…”