Cancer, Inflammation, and Therapy: Effects on Cytochrome P450-Mediated Drug Metabolism and Implications for Novel Immunotherapeutic Agents

Immune system activation through innate and adaptive systemic mechanisms is critical for protection from pathogens and other antigens. However, uncontrolled systemic inflammation may occur as a consequence of acute and chronic conditions and has multiple clinically relevant effects. Inflammation and cancer are fundamentally linked during development, invasion, and metastasis, yet, paradoxically, many cancers evade immune system detection. Components of cancer inflammation include chemokines, prostaglandins, and cytokines, and these have been shown to downregulate cytochrome P450 (CYP) enzyme activity. Recently, promising novel anticancer agents that upregulate immune responses have entered into clinical practice and have shown high response rates. These agents, either alone or in combinations, may cause systemic immune-related adverse events, with potential clinical implications for use of concurrent agents metabolized by CYP and other pathways. In this article, the authors focus on what is known about inflammation, cancer, and CYP-mediated drug metabolism; discuss clinical and pharmacologic data regarding novel immunomodulators; and consider their potential interactions with concurrent agents.