Despite significant research progress on the pathogenesis, molecular biology, diagnosis,
treatment, and prevention of cancer, its morbidity and mortality are still high around the
world. The emerging resistance of cancer cells to anticancer drugs remains still a significant
problem in oncology today. Furthermore, an important challenge is the inability of anticancer
drugs to selectively target tumor cells thus sparing healthy cells.
One of the new potential options for efficient and safe therapy can be provided by opioid
growth factor (OGF), chemically termed Met-enkephalin. It is an endogenous pentapeptide
(Tyr-Gly-Gly-Phe-Met) with antitumor, analgesic, and immune-boosting properties. Clinical
trials have demonstrated that OGF therapy alone, as well as in combination with standard
chemotherapies, is a safe, non-toxic anticancer agent that reduces tumor size.
In this paper, we review the structure-activity relationship of OGF and its analogues. We
highlight also OGF derivatives with analgesic, immunomodulatory activity and the ability to
penetrate the blood-brain barrier and may be used as safe agents enhancing chemotherapy efficacy
and improving quality of life in cancer patients.
The reviewed papers indicate that Met-enkephalin and its analogues are interesting candidates
for the development of novel, non-toxic, and endowed with an analgesic activity anticancer
drugs. More preclinical and clinical studies are needed to explore these opportunities.