Morphine: double-faced roles in the regulation of tumor development

Morphine, a highly potent analgesic, is one of the most effective drugs for the treatment of severe pain associated with cancer. It directly acts on the central nervous system to relieve pain, but also cause secondary complications, such as addiction, respiratory depression and constipation due to its activities on peripheral tissues. Besides pain relief, morphine is of great importance on cancer management with its effect on tumor development being the subject of debate for many years with some contradictory findings. Morphine has shown both tumor growth-promoting and growth-inhibiting effects in many published research studies. And various signaling pathways have been suggested to be involved in these effects of morphine. Based on a thorough literature review, we summarized the double-faced effects of morphine in tumor development, including tumor cell growth and apoptosis, metastasis, angiogenesis, immunomodulation and inflammation. And we attempted to optimize morphine administration in cancer patients to attenuate its tumor growth-promoting effects.