Is nuclear factor kappa-B the missing link between inflammation, cancer and alteration in hepatic drug metabolism in patients with cancer?
In the last few years, several studies have provided a causal link between constitutive activation of nuclear factor kappa-B (NF-kappaB) and the initiation and development of cancer. More recently, it appears that a cancer-induced inflammatory response may be an important factor in the inter-individual variability of the response to and toxic effects of cancer chemotherapy, as well as in the alteration of drug metabolism enzyme expression in patients. The relationships between chronic inflammation (or infection), cancer and drug metabolism are many: chronic infections lead to inflammation, inflammation may lead to cancer, cancer usually leads to an inflammatory syndrome, and inflammation alters the expression of drug metabolising enzymes and thus of the efficiency of cancer chemotherapy. This review focuses on the functional consequences of NF-kappaB activation during oncogenesis and on the expression of the major cytochrome P450s (CYP) involved in anticancer therapies. Finally, the potential role of NF-kappaB as the missing link between inflammation, cancer and alteration in hepatic drug metabolism in patients with cancer is discussed.
Assenat
Eric
E
CHRU Montpellier, Hôpital Saint Eloi, Service Hépato-Gastroentérologie, Montpellier F-34295, France.
Gerbal-chaloin
Sabine
S
Maurel
Patrick
P
Vilarem
Marie José
MJ
Pascussi
Jean Marc
JM
D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D016328:NF-kappa B / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology
D016328:NF-kappa B; D003577:Cytochrome P-450 Enzyme System