Chapter 22: Role of kynurenine pathway in neuro-oncology

Abstract

Despite decades of research, both primary and metastatic brain tumors remain intractable clinical problems. While the kynurenine (KYN) pathway of tryptophan metabolism has been well explored in other cancer types, there are few studies of human brain tumors. The rate-limiting enzymes of the conversion of tryptophan to kynurenine (both forms of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO2)) have been studied predominantly in gliomas with in vitro methods, in vivo animal studies, and ex vivo tissue studies of surgically resected specimens. In these studies, IDO1 has been shown regulated by interferon-γ (as in other cancer types) and TDO2 by the glucocorticoid receptor. IDO and TDO2 have also been positively correlated with tumor grade and negatively correlated with patient survival in glioma. One seminal study also identifi ed KYN as an activator of the aryl hydrocarbon receptor (not previously shown in any other cancer types). Therefore, the KYN pathway may represent new opportunities for treatment strategies for brain tumors.