Role of Relaxin Signaling in Cancer: A Review

[Display omitted] The investigation into relaxin (RLN), additional RLN-like proteins, and RLN family peptide receptors (RXFP) has demonstrated their role in modulating the extracellular matrix (ECM), immune cells, specifically macrophages, and angiogenesis, with recent evidence showing an effect on signaling pathways in tumor cells. These findings serve as the basis for our narrative review to collate pertinent studies in this field and provide our perspective on their clinical and investigational significance. In the article, we discuss findings from pertinent studies focusing on evaluating the expression or effect of RLN1, RLN2, or RXFP1 in various cancers. We also briefly discuss the potential role that other RLN family peptides and their receptors play in cancer. Specifically, we delve into questions regarding RLN signaling in terms of parity/pregnancy-associated protection from mammary tumors, expression in tumors, detection in serum in the setting of cancers, effect on tumor-adjacent cells, effect on tumorigenesis depending on endogenous expression or delivery, and last, but not the least, impact on the effectiveness of anti-cancer therapies. We expect that summarizing the available literature to answer these questions will allow readers to understand the role of RLN-receptor interaction in cancer as well as identify areas of uncertainty and avenues for future investigation.