Adenosine, Schizophrenia and Cancer: Does the Purinergic System Offer a Pathway to Treatment?

Abstract

For over a century, a complex relationship between schizophrenia diagnosis and development of many cancers has been observed. Findings from epidemiological studies are mixed, with reports of increased, reduced, or no difference in cancer incidence in schizophrenia patients. However, as risk factors for cancer, including elevated smoking rates and substance abuse, are commonly associated with this patient population, it is surprising that cancer incidence is not higher. Various factors may account for the proposed reduction in cancer incidence rates including pathophysiological changes associated with disease. Perturbations of the adenosine system are hypothesized to contribute to the neurobiology of schizophrenia. Conversely, hyperfunction of the adenosine system is found in the tumor microenvironment in cancer and targeting the adenosine system therapeutically is a promising area of research in this disease. We outline the current biochemical and pharmacological evidence for hypofunction of the adenosine system in schizophrenia, and the role of increased adenosine metabolism in the tumor microenvironment. In the context of the relatively limited literature on this patient population, we discuss whether hypofunction of this system in schizophrenia, may counteract the immunosuppressive role of adenosine in the tumor microenvironment. We also highlight the importance of studies examining the adenosine system in this subset of patients for the potential insight they may offer into these complex disorders.

Genetic prediction of the causal relationship between schizophrenia and tumors: a Mendelian randomized study

“…Schizophrenia is a serious mental illness that affects the thinking, behavior, and emotions of patients (1). Recent studies have demonstrated a complex relationship between schizophrenia and tumor incidence (2).…”

“…Understanding this relationship may help us better understand the pathological mechanisms of schizophrenia and provide new implications for future treatment strategies. The relationship between schizophrenia and tumors is complex and delicate (2). Further research is needed to explore and understand this relationship to provide a scientific basis for the prevention and treatment of schizophrenia and tumors.…”

Purinergic Signalling in Physiology and Pathophysiology

“…The review by Hamoud et al [7] explores the potential relationship between adenosine, schizophrenia, and cancer. They detail the incidence of cancer in schizophrenia, extracellular adenosine metabolism, adenosine receptor signaling and uric acid metabolism, before outlining the evidence for adenosine system perturbations in schizophrenia, and the role of extracellular adenosine generation in cancer and its potential as a therapeutic target in this disease.…”