Ghrelin is an endogenous
peptide hormone mainly produced in the stomach. It has been known to regulate energy homeostasis, stimulate secretion of
growth hormone, and mediate many other physiologic effects. Various effects attributed to
ghrelin contribute to many aspects of
cancer development and progression. Accordingly, a large body of evidence has emerged about the association of
ghrelin with several types of
cancer in scales of cell-line, animal, and human studies. However, existing data are controversial. This controversy occurs in two main domains: one is the controversial results in local effects of
ghrelin on different types of human
cancer cell-lines; the second is the apparent disagreement in the results of in-vitro and clinical studies that investigated
ghrelin association to one type of
cancer. These inconsistencies have hampered the indications to consider
ghrelin as a potential
tumor biomarker or therapeutic agent in
cancer patients. Previous studies have reviewed different parts of current literature about the
ghrelin-
cancer relationship. Although they have highlighted these controversial results in various ways, no specific recommendations have been given to address it. In this study, we comprehensively reviewed in-vitro, in-vivo, and clinical studies and attempted to use the following approaches to unravel the inconsistencies detected: (a) to distinguish local and systemic effects of
ghrelin in interpreting its summary clinical role in each
cancer; (b) scrutinizing factors that regulate local effects of
ghrelin and could justify different effects of
ghrelin on different
cancer cell-lines. These approaches could have notable implications for future in-vitro and clinical studies.