Spoken and Unspoken Matters Regarding the Use of Opioids in Cancer

Pain is among the most debilitating symptoms in patients with cancer. Except for their relatively frequent use during end-of-life care, opioids are often, though not routinely, prescribed during the course of the disease. Whereas the clinical phenomena of tolerance, dependence, and addiction are invariably recognized, the molecular mechanisms which effect these outcomes are not fully understood, even among health care professionals. Also uncertain is the possible unfavorable effect of these agents on cancer progression and survival, an association that may be related to the expression of opioid receptors in some tumors. An intriguing corollary of the latter finding is that cancer cells may also manifest equivalents of the three maladaptive phenomena. Accordingly, instead of re-addressing the societal and epidemiological impact of opioids, this paper has three alternative foci. The first, and most subordinate, focuses on the mu opioid receptor; the second, centers on the unresolved question regarding the potential adverse effect of opioids on tumor growth; the third, and most compelling, concentrates on the cellular apparatus and influences that modulate tolerance, dependence, and addiction in certain cancers exposed to opioids.