Opioid utilization for pain management is prevalent among cancer patients. There is significant evidence describing the many effects of opioids on cancer development. Despite the pivotal role of metabolic reprogramming in facilitating cancer growth and metastasis, the specific impact of opioids on crucial oncogenic metabolic pathways remains inadequately investigated. This review provides an understanding of the current research on opioid-mediated changes to cellular metabolic pathways crucial for oncogenesis, including glycolysis, the tricarboxylic acid cycle, glutaminolysis, and oxidative phosphorylation (OXPHOS). The existing literature suggests that opioids affect energy production pathways via increasing intracellular glucose levels, increasing the production of lactic acid, and reducing ATP levels through impediment of OXPHOS. Opioids modulate pathways involved in redox balance which may allow cancer cells to overcome ROS-mediated apoptotic signaling. The majority of studies have been conducted in healthy tissue with a predominant focus on neuronal cells. To comprehensively understand the impact of opioids on metabolic pathways critical to cancer progression, research must extend beyond healthy tissue and encompass patient-derived cancer tissue, allowing for a better understanding in the context of the metabolic reprogramming already undergone by cancer cells. The current literature is limited by a lack of direct experimentation exploring opioid-induced changes to cancer metabolism as they relate to tumor growth and patient outcome.
Keywords: TCA; cancer; glycolysis; metabolic pathway; metabolomics; morphine; opioid; tumor.