Selective COX-2 inhibitors as chemopreventive and therapeutic
agents

Hb, Grossman

doi:10.1358/dot.2003.39.3.799454

Cited by 13 publications

(6 citation statements)

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“…The first description of inverse association between aspirin use and the risk of CRC was published in 1988 . Although the underlying mechanism has yet to be defined, NSAIDs are believed to prevent CRC mainly by inhibiting COX‐2 . Although COX‐2 is undetectable in the normal gastrointestinal epithelium, it is detectable in 40% of colorectal adenomas and in more than 80% of CRC .…”

Section: Candidate Agents For Crc Chemopreventionmentioning

confidence: 99%

Chemoprevention of colorectal cancer: Past, present, and future

et al. 2019

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Chemoprevention began to be considered as a potential strategy for lowering the incidence of cancer and cancer‐related deaths in the 1970s. For clinical chemoprevention trials against cancer, including colorectal cancer (CRC), well‐established biomarkers are necessary for use as reliable endpoints. Difficulty in establishing validated biomarkers has delayed the start of CRC chemoprevention development. Chemoprevention trials for CRC have only recently been initiated thanks to the identification of reliable biomarkers, such as colorectal adenomas and aberrant crypt foci. Some promising agents have been developed for the prevention of CRC. The chemopreventive effect of selective cyclooxygenase 2 inhibitors has been shown, although these inhibitors are associated with cardiovascular toxicity as a crucial adverse effect. Aspirin, which is a unique agent among non‐steroidal anti‐inflammatory drugs (NSAIDs) showing minimal gastrointestinal toxicity and no cardiovascular risk, has prevented adenoma recurrence in some randomized controlled trials. More recently, metformin, which is a first‐line oral medicine for type 2 diabetes, has been shown to be safe and to prevent adenoma recurrence. A recommendation of the United States Preventive Services Task Force published in 2016 provides a Grade B recommendation for the use of aspirin for chronic prophylaxis against diseases, including CRC, in certain select populations. However, the roles of other agents have yet to be determined, and investigations to identify novel “post‐aspirin” agents are also needed. The combined use of multiple drugs, such as aspirin and metformin, is another option that may lead not only to stronger CRC prevention, but also to improvement of other obesity‐related diseases.

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Section: Candidate Agents For Crc Chemopreventionmentioning

confidence: 99%

Chemoprevention of colorectal cancer: Past, present, and future

et al. 2019

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“…Aspirin, a non-steroidal anti-inflammatory drug (NSAID) has been shown to correlate with a decreased risk of developing cancer, particularly preventing colorectal cancer (CRC) [ 113 , 114 ]. The majority of the studies are observational in nature and the mechanisms are currently being investigated; however, it is believed that aspirin may prevent CRC by inhibiting COX-2 [ 115 ]. This ultimately led to the development of a new class of NSAIDs that are more selective for COX-2 inhibition for use as chemopreventive agents.…”

Section: Introductionmentioning

confidence: 99%

Targeting AMPK for cancer prevention and treatment

et al. 2015

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AMP-activated protein kinase (AMPK) is an important mediator in maintaining cellular energy homeostasis. AMPK is activated in response to a shortage of energy. Once activated, AMPK can promote ATP production and regulate metabolic energy. AMPK is a known target for treating metabolic syndrome and type-2 diabetes; however, recently AMPK is emerging as a possible metabolic tumor suppressor and target for cancer prevention and treatment. Recent epidemiological studies indicate that treatment with metformin, an AMPK activator reduces the incidence of cancer. In this article we review the role of AMPK in regulating inflammation, metabolism, and other regulatory processes with an emphasis on cancer, as well as, discuss the potential for targeting AMPK to treat various types of cancer. Activation of AMPK has been found to oppose tumor progression in several cancer types and offers a promising cancer therapy. This review evaluates the evidence linking AMPK with tumor suppressor function and analyzes the molecular mechanisms involved. AMPK activity opposes tumor development and progression in part by regulating inflammation and metabolism.

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“…Selective Cyclooxygenase 2 (Cox-2) inhibitors have received increasing attention for their potential usage as chemopreventive and therapeutic agents in cancer treatment [1][2][3][4][5][6]. Ongoing clinical trials will determine whether Cox-2 specific inhibitors will be useful in the treatment different types of cancer.…”

Section: Introductionmentioning

confidence: 99%

Cyclooxygenase-2: Potential Role in Regulation of Drug Efflux and Multidrug Resistance Phenotype

Sorokin¹

2004

CPD

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Multidrug resistance (MDR) of cancer cells to cytostatic agents is the major obstacle for the succesfull chemotherapy. One of the causes of the development of cellular resistance to a wide variety of drugs is the elevated expression of membrane transporter proteins such as members of ATP binding cassette (ABC) protein superfamily. Expression of the ABC transporter MDR1, also termed P-glycoprotein (P-gp), seems to correlate with drug resistance of tumors to chemotherapy. Cyclooxygenase-2, an inducible isoform of enzyme, responsible for generation of prostaglandins from arachidonic acid, is constitutively expressed in a number of cancer cells. Anti-cancer potency of cyclooxygenase inhibitors is established, but the mechanism of Cox-2-dependent potentiation of tumor growth is a subject of intense discussion. Here we focus on the discussion of potential link between Cox-2 expression and development of multidrug resistance phenotype. Our observation, that enforced expression of Cox-2 causes enhancement in MDR1 expression and functional activity suggests the existence of causal link between Cox-2 activity and MDR1 expression. The use of Cox-2 inhibitors to decrease function of MDR1 may enhance accumulation of chemotherapy agents and decrease resistance of tumors to chemotherapeutic drugs.

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Selective COX-2 inhibitors as chemopreventive and therapeutic agents

Cited by 13 publications

References 0 publications

Chemoprevention of colorectal cancer: Past, present, and future

Chemoprevention of colorectal cancer: Past, present, and future

Targeting AMPK for cancer prevention and treatment

Cyclooxygenase-2: Potential Role in Regulation of Drug Efflux and Multidrug Resistance Phenotype

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