Friend or Foe? An Unrecognized Role of Uric Acid in Cancer Development and the Potential Anticancer Effects of Uric Acid-lowering Drugs

Abstract

In recent years, metabolic syndrome (Mets) has been a hot topic among medical scientists. Mets has an intimate relationship with the incidence and development of various cancers. As a contributory factor of Mets, hyperuricemia actually plays an inseparable role in the formation of various metabolic disorders. Although uric acid is classically considered an antioxidant with beneficial effects, mounting evidence indicates that a high serum uric acid (SUA) level may serve as a pro-oxidant to generate inflammatory reactions and oxidative stress. In this review, we describe the unrecognized role of hyperuricemia in cancer development and summarize major mechanisms linking uric acid to carcinogenesis. Furthermore, we also discuss the potential mechanism of liver metastasis of cancer and list some types of uric acid-lowering agents, which may exert anticancer effects.

Serum Uric Acid Levels and Risk of Eight Site-Specific Cancers: A Mendelian Randomization Study

“…Chronic inflammation and tissue infiltration by neutrophils, macrophages and monocytes ( Grainger et al, 2013 ; Weigt et al, 2017 ), in turn, promote carcinogenesis ( Fini et al, 2012 ; Braga et al, 2017 ; Ahechu et al, 2018 ). Due to the complex roles UA plays in cancer occurrence, associations remain unconfirmed in previous epidemiological literature ( Strasak et al, 2007 ; Dziaman et al, 2014 ; Horsfall et al, 2014 ; Szkandera et al, 2015 ; Battelli et al, 2016 ; Mi et al, 2020 ).…”

“…This pathway was found to be protective from ROS-induced damage and cancer pathogenesis in humans ( Itahana et al, 2015 ). In contrast, UA levels are also regarded to be a risk factor for cancer due to its function in inducing chronic inflammation and increasing ROS production ( Mi et al, 2020 ). Chronic inflammation and tissue infiltration by neutrophils, macrophages and monocytes ( Grainger et al, 2013 ; Weigt et al, 2017 ), in turn, promote carcinogenesis ( Fini et al, 2012 ; Braga et al, 2017 ; Ahechu et al, 2018 ).…”

Phase II Trial of Sipuleucel-T and Stereotactic Ablative Body Radiation for Patients with Metastatic Castrate-Resistant Prostate Cancer

“…Increased uric acid levels have been shown in the literature to be a poor prognostic marker for advanced gastric cancer patients [ 40 ]. While uric acid acts as an anti-oxidant via scavenging free radicals, abnormal plasma levels trigger inflammation and oxidative stress [ 41 , 42 ]. There is some evidence to support that hyperuricemia leads to dysregulated T cell proliferation and can affect the response of cancer to immunotherapy [ 41 , 42 ].…”

“…While uric acid acts as an anti-oxidant via scavenging free radicals, abnormal plasma levels trigger inflammation and oxidative stress [ 41 , 42 ]. There is some evidence to support that hyperuricemia leads to dysregulated T cell proliferation and can affect the response of cancer to immunotherapy [ 41 , 42 ]. Therefore, it remains to be evaluated if higher levels of plasma uric acid played any causative role in patients failing to respond to this regimen.…”

Does Hyperuricemia in Falciparum Malaria Infected Children Explains the Etiology of Burkitt’s Lymphoma?

“…These metabolites can overwhelm the body's normal homeostatic mechanisms and form urinary crystals and precipitates that cause ARF [1]. Serum uric acid in very high concentrations may trigger inflammatory stress, and it may also have intracellular pro-oxidative activity [2].…”